Gene Sherpas: Personalized Medicine and You

The case for hippocratic oath in web health services

2012-01-08T10:49:00.000-08:00

Today I want to tell you why I think that health related applications on the internet should have not only some "Good Housekeeping Seal of Approval" but should also take an oath similar to the one I took when I graduated from medical school.

On it's face, there will likely be 3-4 camps reading this. One will automatically dismiss this as the "Web services" aren't providing diagnosis or treatment. My counter to them is that I said "similar to" the hippocratic oath I swore to. We'll call it the HippocraticWeb oath.

The second camp of people will say "This is a fantastic idea but aren't there services like this that certify web content?" My answer to them is that this is not a certification of web content. Further, we all know those services like HONcode that certifies trustworthy information. Instead this will act as a code of ethics which the consumer of the health service will understand to mean a reputable business who has taken an oath which will work in the interests of the consumer.

The third camp will say "Shouldn't the government be doing this?" My answer is: It hasn't. And how could one government govern the world and the internet? That is foolish. Instead, the web should do as those in the professions have done. Govern themselves with codes of honor and oaths which are publicly available. And no I don't mean "Don't be evil"

I mean a certifiable oath that speaks about the actions of the business housing your health and medical data. I mean an oath that governs corporate decision making about whom to sell or share your data with. Not in a way that will make them the most money, but in a way that protects you, the person. After all, you paid to have access to your data, whether that be an LDL cholesterol, a blood pressure, a REM sleep cycle, a whole genome or what have you.

Why do we need such a code?

In my Nature Biotech piece I explain the dilemma with using web services for health purposes. Corporate interests are not designed primarily for the benefit of customers. They are primarily designed for the benefits of the corporation, whether that be 23andMe who just made a hash of an unnanounced TOS change (In this way there should be an offset to consumer.Which 23andSerge finally came around to because of public outcry)

Or it be flagrant sharing of your data without your permission through privacy leaks or hacking. (IMHO Insurers should have given millions of dollars back to members for their leaks and gaffes)

Why? Health companies have to do this already. But where does that money go? Further, how do I know that someone will do the right thing with my data when there is a breach? This Oath would allow the best of class to accept responsibility for their actions.

Don't think it doesn't happen? Check it out here. And this exempts companies like 23andMe or Livestrong.com. Why. Because they are not governed by HIPAA or HiTECH!

I am not proposing further regulation here. All I am asking for is that these businesses purporting to help us maximize our health "Man Up" so to speak and all swear an Oath, The HippocraticWeb Oath.

The HippocraticWeb Oath

I swear by that which I hold most sacred, that I will fulfill according to my ability and judgment this oath and this covenant:

I will apply reasonable measures to protect the welfare of the customers whose information I keep; I will keep in mind that this data they have granted me access to is theirs. Should I wish to own this, I will compensate the customer fairly.

I will neither use this data as means of blackmail or coercion of customer. Nor will I engage in business with a company who has or intends to.

I will not use the information in a legal proceeding unless receiving subpoena and properly notifying the customer of such request. In reasonable and fair time frame to the customer.

I will not change terms or service, business plans or custodians of data without giving proper notice to affected customers, allowing them time to air grievances prior to making the business decision.

What I may see or hear in the course of business in regard to the life of customers, which on no account one must spread abroad, I will keep myself holding such things shameful to be spoken about.

If I fulfill this oath and do not violate it, may it be granted to me to enjoy life and art, being honoured with fame among all men for all time to come; if I transgress it and swear falsely, may the opposite of all this be my lot inclusive of compensation to my customers.

That's it. Who would be averse to having something like this? It is a simple statement ensuring that the people who have access to your data will use it properly and compensate you if the transgress.

If you believe in what I am proposing please email me steven(dot)murphy(at)Greenwichdocs(dot)com I am currently working out how to implement this very important piece of trust into corporate ethic and standards when it comes to health and medical companies that provide health and medical services over the internet. This company should not be owned or part of any corporate consortium to "Get out in front" of this. Rather it should be a non for profit headed by a well balanced board of advisors. So, are you interested?

Warmly,

Steven A.R. Murphy MD

p.s. That 4th camp is full of people like me!

23andMe Buyer Beware, The Internet doesn't equal hippocrates

2012-01-06T13:47:00.000-08:00

Ok, ok. I am not gonna tell you I told you so. But, I did.
Did anyone read my article in Nature Biotechnology? Did ya?

Here is your freaking reality check. 23andME has your DNA. It has it hostage and it has your datapoints. And it can do whatever the hell it pleases. Including locking or cancelling your account.

They have enough data points for their robust database. They only need you sheep to keep paying 9 dollars per month or 108 dollars per year and 99 to start. 10 years? 1080 dollars. Even more than the first 999 USD they started with.

Well guess what? People everywhere are waking up to the charlatanism that was peddled by Silicon Valley Overlords.....

They have you, you are stuck. You have to pay FOREVER!!!!! BWAHAHAHAHAHAHAHAHAHAHAHA!!!!!!

Even if you quit, they don't care. They Pwned you. And they still do.

So what did the Sherpa say all of those years? Huh? No, not that their health reports are bull $hi!. But I did say that. No not that I was done posting on 23andMe. Clearly I am not.

But I told you about the Master Plan!

Even if you pull out your data, they still have it. End of story. You are powerless and have been duped. I am sorry. I wish you had listened

The Sherpa Says: Buyer Beware web sites giving you tests and testing your DNA. 23andMe and its company are not to be trusted. Sorry, but the web has not take the hippocratic oath!

2011 Comes to a close. What we know about Personalized Medicine

2011-12-20T17:56:00.000-08:00

I wanted to write a wrap up of what we know in the last 4 years regarding personalized medicine

1. In regards to DTC Genetics, the FDA won't shut you down if you are google. But you will have to give your test away for free to build your database

2. In regards to Pharmacogenomic testing, most doctors won't use the service despite studies showing utility that have existed for 2 years.

3. In regards to GWAS predisposition testing, it is mostly useless. It doesn't scare or heal you.......most of the time

4. Classical Cancer Genetics, Cardiogenetics, GI Genetics and preconception genetics have growing concerns as I am seeing more and more of these over the last 2 years.

5. When Whole genome or exome testing come out, we will have a mess load of data. This is an opportunity if someone can create subtractive algorithms to the "normal" data. Which may help us out....IFF we have a true "Normal Genome"

6. The Sherpa has been slow in posting, but these points are facts now.

The Sherpa Says: 4 years, a lot of hype, lots of sideways climbing. Next year will show big moves, just like 2007/2008 and we'll still be here.

Back again, 23andMe still $hits the bed with their reports

2011-09-03T13:39:00.001-07:00

In case you haven't noticed. I dropped off the blog radar for a while. I had some growing to do of the practice and some streamlining. I read Daniel MacArthur's post with great interest this week. It describes clinical utility of 23andMe testing......

The one thing I haven't stopped doing is counselling patients on DTC Genomic reports.

Just yesterday I was consulting a very nice patient. They told me they just had to speak with a doctor because the report indicated that they were at increased risk of stomach and esophageal cancer. They had been up for several nights reading about it. Further, when brought to their PMD, the PMD smiled and didn't offer up any advice.

Well, first let me preface by saying, 23andMe's SNPs which they list 4 huge freaking stars of "CON"fidence for, on Esophageal and Stomach Cancer risk, while BTFW only ranking studies on Han Chinese. And only 2 studies at that.......

This report had this patient seriously concerned. Until of course I took a G-D Damn pedigree and found out they had ZERO, I repeat ZERO Asian ancestry/ethnicity, let alone Han Chinese....

The risk report from 23andSerge listed them as high risk. How in the world did that work?

(BTW, if you don't believe me, just ask and I will send you the time stamped pdfs, with name redacted of course)

You know why that worked? Because the brainchildren at the Google owned company forgot to put an ethnicity/ancestry filter on their reports. Instead they just felt that an asterisk would work just fine.....

Well Guess what 23andMe, you haven't changed at all. Even after the FDA got on your A$$. Your reports still are misleading and are causing undue angst.

Lucky for you, Myself and Dr Lubin are around to pick up after your mess......

Can you see why someone needs to look at and police these reports? This poor patient had serious concerns and when brought to a clinician who couldn't understand the SNP studies could end up with not needed endoscopies which would put the patient at risk. Primarily due to physician malpractice avoidance behavior?

Don't think that hasn't happened? Think Again.

The Sherpa Says: I am back again at it because clearly the millionaires with a penchant for DNA peddling and CPU coding can not get this right......Clearly a #FAIL

Non-Clinician Misinterpretation of DTC Genetic testing

2011-03-25T14:06:00.000-07:00

Ok,

In case you haven't all figured it out. Blogs are dead. Mine is too, sorta. I have less and less time to blog as my practice explodes. But there are some things that just merit a blog post.

I am on twitter, you can follow me there @genesherpas

But now I am on the Sherpa. Yes, the blog that nearly got me on 60 Minutes and definitely won me the hearts of USA Today to be interviewed...BTW the practice got super busy after that......

Today I want to talk about something more serious.

The FDA hearings have laid the course clear. Direct To Consumer Genetic testing will be regulated.

Why?

1 part potential harm

2 parts irreverence for laws and medical regulation

3 parts flagrant misrepresentation of what genetic tests can do.......

See Kari S. Disavowal of his company's stupid tag line.......

Today on twitter Shirely Wu @shwu retweeted something that was the picked up by @dgmacarthur..... great geneticist, but not a medical geneticist........

That was:

A thoughtful and eloquent case-study petition to keep genetic testing DTC:http://bit.ly/dL3qar from @celticcurse #FDADTC

The problem?

I respect Shirley a lot, but this article is not thoughtful, nor is it eloquent.

Instead it is full of misinterpretation and IMHO an ignorance of the role of genetic testing in hereditary hemochromatosis.....

In no way is HFE genetic testing required or indicated to pick up a person with hereditary hemochromatosis.

USPSTF says the harms outweigh the risks of genetic testing for screening

There are multiple genes involved in hereditary hemochromatosis only testing HFE and thinking you are "off the hook" is stupid.....

There are also modifier genes likely too.....

In other words, perhaps the cheerleaders for DTCG are misinformed about the true utility of this type of testing. Further, if they knew the literature, perhaps they would be less angry that the FDA(who know the data BTW) want to regulate against these types of misinformed claims that could lead to misinterpretation by consumers and end up fleecing their pockets for fools gold.

Let's take this little gem from @celticcurse

"A simple genetic test is all it takes to know if hereditary hemochromatosis, the most common genetic killer in America, is in your genes."

Bull$h!t buddy.....less than 30% of HFE variant persons ever develop the disease. Do me a favor, partner with a doctor to hack your health next time please......

In case you wondered, iron studies are the key to screening. I get them in every northern european or any family history of liver disease, gonadal failure, arthritis, etc......

But, the lab heads wouldn't know that. Which is why lab heads shouldn't release discoveries into the wild......

The Sherpa Says: This retweet blog post by CelticCurse is an eloquent reason WHY DTC genetic testing should be regulated for claims and use......regulate the medical as a medical test, let the ancestry buffs do their thing sans FDA. End of story guys.....

Coriell and OSU integrate GWAS into an EMR!

2011-02-02T18:04:00.000-08:00

Ok, so enough with the acronyms.....

I am back and will be blogging more often again. So for those who still lurked around, tell the others that the Howard Stern of Genomics is back. I took a social networking holiday for a solid 2 months, plus the addition of having my practice change quite a bit after my USA Today and follow ups in the local papers.....

Today I want to announce that Coriell Personalized Medicine Collaborative and Ohio State University will be using data from an arm of the CPMC and OSU to integrate genetic risk data into the medical record.

Correct me if I am wrong, but I don't know of anyone else doing this exact same thing.

Ideally they will also continue to roll things in like PGx data. (I know this data will be coming soon)

By integrating things like Plavix response, you can make more gametime decisions easily.

I.E. Patient presents to the ED with a heart attack. Armed with prior knowledge about plavix nonresponder, you pick Effient.

What is so awesome about this arm is that Primary Care Physicians, Cardiologists AND patients will be participating and receiving results.....

They will be studying the behavior and knowledge of participants in the study, we have seen other data on this sort of thing, I wonder if we will see the same thing here.

For risk data? Probably. For PGx Data? Probably not.

Why? A plavix response in the medical record is a game changer.

3 Reasons

1. The clinician will be hit in the face with a "Plavix doesn't work here"

2. The physician may even find they are a nonresponder

3. There has got to be some hustling attorney out there, who will be lurking once they see the CPMC/OSU release. I am certain at least the physicians will be thinking so.....

You can read the Presser Here

The Sherpa Says: Study of clinical use and behaviors will be key to know how vital this data is and thus how tightly we should regulate its use in medical records i.e. 23andMe clinical BRCA testing! P.S. Like our new crest?

Genetic test may refine PSA or it may not!

2010-12-21T05:26:00.000-08:00

I am going to read this article for the seventh time and get back to you this week.

In case you missed it, the PR Firm hired by DeCode pumped out a presser (press release), which I refuse to link to directly.....which essentially said

"Analysis of Four SNPs, in Tandem With Genetic Risk Factors Detected by the deCODE ProstateCancer(TM) Test, Yields Substantial Improvement in Efficacy of PSA Screening"

OK, 4 SNPs tells us whose PSA value is a bad 2.8 vs. good 5.8?

Or at least that's what the Kari S. tells us

"This is straighforward genetics with direct clinical utility." -Kari S. (Yes they rushed the release out with the misspelling of "straightforward")

Ok, so tell me, how has this straightforward genetic test performed in a prospective analysis?

What do you mean you haven't done that yet? So how can we have you assert that there is direct clinical utility?

We can't. Maybe you meant STRAY FORWARD?

Secondly, this study was carried out on Caucasian men, leaving African Americans, who often have earlier and more aggressive prostate cancer out in the dark.......

But what really got my Ire was when respected Tweeters started parroting this presser.........

Here is some high heat for us genome critics, read the study and read the presser. If the presser hypes the study, we should tear it apart and present the true facts for all to see on the internet.

Read and analyze the study, not the presser. I know we are all busy these days, but we owe that to our readers and the public. Hell, that makes us even better than a whole host of journalists who seem to quote Kari as if his opinion is the final take.

The Sherpa Says: On seventh read I will have a take on what these "SNPs that strengthen the predictive power of PSA" really mean.

23andKari, what the 99 USD subsidy means for Personal Genomics

2010-11-30T05:49:00.000-08:00

Yes, Yes.....

Everyones' little heart is a-twitter for the subisdized cost of 23andSerge, now to be known as 23andKari (will tell you why soon) a whopping 99 USD. Which I had been saying is the correct price point for about 2 years now.

Yes, finally, something other than a blimp and million dollar parties will actually pull out the lurkers.....

Here's my take. There was a company in a galaxy far far away, Iceland. That was the toast of the town in 2004. Why? They were collecting genomes for a grand experiment. They were going to discover fantastic links to disease and sell access to the highest bidder.

While they did produce some great Nature papers......what happened to DeCode?

I think we all know.

23andKari has now emerged. The front end.....happy shiny ancestry and disease links.....

I have forgotten to mention that the FDA still hasn't finished working on these companies, have I?

The back end? A database of genomes to cull for disease links to be sold at the highest bidder?

Sound familiar??

In case you forgot, Kari did this with Gulcher and went belly up.......

And BTW, who owns that genetic data now? Is it getting resold?

Celera too?

Also in case you forgot, this is a rock bottom version of Navigenics game...How's that working?

I think 23andKari will actually survive. Why? Huge megacorporation investment. That's why.

GOOG et.al. own 23andKari now. Your data? Wrong! Theirs. Now that they are being investigated for antitrust in the EU, they have to move quickly on this phase......

I have said it before and will again. Why sell Manhattan for bobbles and trinkets?

Because it's cheap, that's why........Hell. IMHO, 23andKari should be paying you for your genome.

I hope the lab 23andKari is using is up to snuff this time.....after that whole sample swap issue, they are about to get a whole lot more volume.

The Sherpa Says: Democratization is about to go the way of Russia and it's oligarchs...

23andMe going infomercial style!

2010-11-24T09:30:00.001-08:00

Dan Vorhaus points out the Plan B for 23andSerge!

Personally I love the irony of naming it "Plan B"

MSRP 499, but yours for the low, low price of 99 USD.

QVC, here we come!!!!

Respiragene Test and CT Screening for Lung Cancer?

2010-11-18T18:14:00.000-08:00

I love personalized medicine.

I absolutely think it is beyond fantastic to be able to say to a patient "This is the drug for you"

Or, we need to screen for disease X because of Gene Y and your family history

But what I don't love is companies purporting the import of their special home brew test to do personalized medicine without any sort of data backing them up.

A news report and "AACR Feature" highlighted precisely that. A test with no data......

From the article:

Researchers administered a gene-based predisposition test that incorporates 20 genetic markers associated with smoking-related lung damage and propensity to lung cancer along with clinical factors including age, family history and diagnosis of chronic obstructive pulmonary disease to derive a risk score on a 1 to 12 scale with higher scores correlating with higher risk.

Ok, new score with 20 markers, family history and age and clinical data....sounds reasonable. Has anyone else validated this tool????

Ahem. Crickets.....

“At scores of 6 or more … only 25 percent of otherwise eligible smokers would be screened but over half of lung cancers would potentially be detected, many in a treatable stage,” concluded Young and colleagues, who suggested that increasing the detection rate of lung cancer per number of patients screened could improve the cost-effectiveness of CT screening.

Ok, so did you get the jump? Did you catch it? "Who Suggested"

This guy who designed a genetic panel AND NEVER TESTED IT IN CONJUNCTION WITH CT CHEST SCREENING, is suggesting that using the test could increase the cost effectiveness of CT Screening, without one single solitary IOTA or shred of evidence of this.

This would be the same Dr. Young who found that genetic testing for a smoking cessation program likely doesn't have cost effectiveness or at best is uncertain.

Last year they were still researching this panel

Yet Respiragene is being held up as a great test!

One word that makes me suspicious is the word "Testamonials"

That word alone reminds me of the time I was bamboozled into going to multi level marketing events for proton pills and the like. You know, they all had lots of "Research" behind them.

Put simply, we do not know if gene screening PRIOR to CT Chest screening for lung cancer does any of the following things

1. Make CT Screening more cost effective

2. Personalizes medicine, targeting radiation to only those who need the test

3. Improves outcomes and detection rates of lung cancer.

That research is not available today. Nor will it be in one year.

My Advice, hold off on this one for now.

The Sherpa Says: Parroting an esteemed researchers OPINION as if it were scientific fact is a great way to get yourself in trouble and an even greater way to confuse the community! But it is the best way to get a test sold.

Pulitzer Prize Winner Amy Harmon hosting ethical dilemmas!

2010-11-11T17:59:00.000-08:00

How do you face life as a 22 year old if you carry a genetic variant for an incurable illness that will most likely strike in middle age?

That's right,

Amy Harmon is hosting a fantastic course that will be starting November 15th. You better hurry up and register because space is limited and closing on the 14th of November.

What will be covered?

The course will have weekly live online sessions with the instructor as well as self-paced lessons filled with original content covering the weekly topics. All live sessions and course material can be accessed directly within the online course.

Prenatal testing can go into deep detail about an unborn baby’s prospects for the future. How much of this do we want to know? To share?

These questions and more will be addressed. If there is one thing I know. Amy is certainly a fantastic teacher, educator, and discussion leader!

I do miss conversations like those with her!

You too can have that kind of expertise. Register before November 14th!

I am certain you will enjoy this set of topics and have directed many people this way already.

The Sherpa Says: Family history picks up life threatening disease, DTCG tests probably not so much. That being said, what's the ethical quandry with either? Ask Amy and find out!

Consumer Genetic Testing for heart attack risk? Worthless!

2010-11-10T17:50:00.000-08:00

Here are the top ten reasons why in its current state, direct to consumer or otherwise, genomic testing for cardiovascular disease risk is dead in the water

1. Family History Risk paints a far better picture and IT IS FREE

2. Reynolds and Framingham risk paint a more accurate picture

3. An independent panel has reviewed 58 variants, 29 genes, and gave the thumbs down.

4. The highest increased risk from any of these tests is 30%, Fam Hx can be as high as 500%

5. Kif6 was just shot down as a useful marker.

6. Clinical Utility has not been evaluated in ANY of these tests.

7. Spit Parties don't lower cholesterol

8. The FDA is hunting down these type of crazy claims!

9 . Topol's heart attack gene didn't pan out, why would these?

10. A recent 23 gene panel failed to make the grade as well.

Let me be crystal clear.

I am glad that the number one reason for ordering a DTCG test was curiosity and not true medical concern in the "early adopters"

But I am concerned that may not be the case for the next wave. I am concerned they will take these genetic tea leaves and use them.

The problem, most of these tests are disproven or will be in the next couple of years.

Loose associations with small increased risks sounds a lot like fortune telling or phrenology. Or hell, even birth order....

Someday we will have good predictive models, 10-15 years from now. But NOT Now! Do you hear that VC country, SV, NYC, Hedgies?

10 year exit strategy. Not 2 not 8. So stop hyping this bull$h!t and go invest in Gold or Commodities or something for the love of god!

The Sherpa Says: Did you hear the one about the research geneticist? He keeps telling his wife how great their sex life WILL BE! Someday we will have this tool, let's try not to burn out and cynicize the public yet.....HT Francis Collins

Family History Better than Navigenics/DTCG Shill for Cancer Genes?

2010-11-05T18:07:00.000-07:00

Yes,

You heard it here. A recent study abstract and pressed about from my friend Charis Eng MD PhD, Clinical Geneticist, Internist and all around really smart lady spoke today about her findings of a head to head, DTCG vs Family History at discovering cancer risk.

You can watch the webcast about it here!

I actually sent some data Ken Offit's way about a similar thing way back when, Ken is yet another, really smart guy. He wasn't surprised. Nor was I when I heard Dr. Eng's findings.

First, Caveat Emptor

This is an abstract! Repeat after me......

What does that mean?

1. It is not peer reviewed fully

2. It is not published yet

3. It is preliminary data

This test was Navigenics Compass vs Family History in 22 females with breast cancer, 22 males with prostate cancer and 44 people with colorectal cancer.

What was the result? Family History placed far more people in the proper high risk category. 8:1

Family History put 22 people in the appropriate High Risk Hereditary Category, DTCG only one.

Further, it looks to me that the Navi "Gene" Scan missed several high risk patients who actually had MMR mutations (I.E. Genetic Cancer).....D'Oh.

First off, this is like a case study. But it signals a HUGE shortcoming of DTCG. False reassurance.

I have been beating this over the head for 3 years now! These tests that have "medical" relevance need to be couched with proper medical guidance.

I told Mary Carmichael of Newsweek this!

This stuff is medical data and I Told Thomas Goetz of Wired this!

Even the WSJ has gotten it!

There are huge shortcomings in the current offering of DTCG tests and those offering medical information need to be regulated as medical. This is a classic case in point of potential and REAL missed cases.

Not Good.

That being said. It is November AKA Family History Month. You should absolutely take your family history and bring it to your doctor. If they don't know what to do with it, call us. We do.

The Sherpa Says: No surprises Charis, I saw this with some DTC cases I have had, passed it on to Ken who passed it on to NIH and The IOM. This is the huge problem with hype and over promise. It always fails to deliver, unfortunately in this case at a great risk to consumers.

For Personalized Medicine CPMC is the Gold Standard Study

2010-10-27T19:43:00.000-07:00

Ok,

So I just wrapped up a meeting with some, well, nearly all of the most brilliant minds in Pharmacogenomics. Where was I? Yes, on the cover of USA Today's life section.....But where was I really?

Conference? No.

VC event? No.

I was at the Coriell Personalized Medicine Collaborative (CPMC) Pharmacogenomics Advisory Group meeting.

Yes, that sleepy 'Ol Cell Line joint in Camden New Jersey.

I am certain you all know about the CPMC now. But in case you have been sleeping.

Coriell is climbing the mountain, gaining collaborators, building camps. They are essentially doing all the hard work of study analysis so that you don't have to.

Brilliant if you ask me.

Who in the world has the time or money to cull data, looking for important findings?

Google funded "projects", Academic Programs and Not For Profits.

Who do you trust to give you unbiased reports?

NFPs.

Who is the NFP here? Coriell.

Are you curious what the CPMC does?

Why will CPMC win this battle? Even 23andSerge agree that CPMC is the gold standard

1. They have independent advisors and scientists

2. They have nearly all the best independent advisors and scientists

3. They have the support of the government, the community and oh yeah, the FDA isn't investigating them......

4. They have Mike Christman.

5. They have a team who believe in this moral imperative, not a pay check or stock options.

I vowed never to post what transpires at these meetings, but rest assured, it was truly academic heated debate with egos left at the door. This is precisely what you want when someone is going to tell you what your genetic material means for you.

The Sherpa Says: Coriell is on to something here. Something so valuable when the 1000 genomes and the rest of the genomes go public. Someone has to make sense of it all and study what it means......I am proud to be a part of it.

Unregulated DTCG saved my life.

2010-10-21T18:11:00.001-07:00

Ok, so if Ellen Matloff hasn't flipped her bobbed haircut, 99245 without 60 min of MD care-insurance billing head yet, then this story will make her and the rest of the counselors who get mad when untrained MDs do BRCA testing flip out.

A woman's husband on DNADay takes advantage of 23andMe's rock bottom 99 USD fee. Clearly intended to double their database.....which it did

Only to have her HUSBAND open her results and

WHAMMO! You are a BRCA1 carrier! Mazel Tov! Not exactly the "fun" he had been looking for when he saw that flyer.....

Why does Myriad market to doctors? Their stance "We are missing a ton of BRCA mutations out there"

I agree.

So you would think I am happy that an unregulated DTCG testing company that the FDA pilloried finds a medically valid BRCA1 mutation that wasn't suggested by doctors.

Well, here's the shocker.

I am glad they found it.

Yes, thank god someone did before she had ovarian or breast cancer! If she would have, penetrance here is NOT 100% guys......

I am also glad that the woman who had the test was mentally stable enough and smart enough to seek professional help. I wonder what her husband and her do for a living?

I wonder if they are college educated. I wonder if there demographic is anything like the majority of the United States.....probably not....Oh wait. Princeton Grad, Prior Google Grad, CEO....yeah sounds just like my cousin Billy in Dushore PA (FYI I don't have a cousin Billy) But Dushore is in BFE.....

I am not glad that everyone is NOT like Mrs. Steinberg or her husband. In the right hands and with easy access to health professionals this works, sometimes........That is why the FDA has stepped in. Not everyone lives like the Steinberg's

Without professionals and without a level head, this could be a problem.

But the news story re-emphasizes what is crystal clear. This is an unregulated company that delivered a medical diagnostic. This result then drove clinical decision making.

Seriously. The DTCG BRCA test is a medical test. I think the FDA gets that part. Despite what DTCG says.

The Sherpa Says: I am happy for this woman. We need more testing, I agree with Myriad. I also think CGCs should be out teaching doctors rather than letting pharma reps do it. In fact excellent CGCs like Ms. Matloff should never see patients and should instead teach doctors how to do cancer counseling everyday. That is what is needed here, more education given to those who need it. Because clearly the doctors who told Mrs Steinberg (I assume she is AJ) that she wouldn't "need" genetic testing despite the family history of cancer are likely in need of some schooling.

Barbara Evans is Right! Sliding scale of regulation.

2010-10-14T18:51:00.000-07:00

As the FDA debates what they should do, Barbara Evans at the University of Houston Law School and Amy L. McGuire of the Center for Medical Ethics and Health Policy at Baylor College of Medicine in Houston, also includes, Canadian legal expert Timothy Caulfield and Wylie Burke, M.D., of the University of Washington School of Medicine post some guidelines for regulation of DTCG/LDT genetic testing.

I love this sort of handicapping.

You have absolutely brilliant people posing ideas for regulations. I have read a ton. There are those from industry insiders, Ones from industry "Advisors", Ones from politicians who receive funding from industry, Ones from academic centers that do LDT testing. Ones from bioethicists...

But I have paid attention to the mixed group that includes pragmatist Wylie Burke and Barb Evans

In an article I just read from Science published October 8th. They propose rules for DTCG, but I am certain they also would work for LDT.

What they propose is a "sliding scale of potential harm"

Which is sort of what I had been saying for years, which perhaps is why it rings true.

If this is for earwax type, let it go to market, if it is for medically related decision making, probably needs some regulation.

The proponents for a wild west DTCG (WWDTCG), which BTW includes a "registry" say
"Well, there is no proof of harm or risk"

I say, well, this is not about psychologic risk.

Instead, it is about medically actionable risk.

I say this because recently, Kif6 testing has fallen into question, despite a company promoting these tests to physicians.

The test is marketed as a "Statin response" genetic test.

Can you imagine how many people were started on statins? Well, 250,000 tests had been ordered. Even if 10% were started it would be nearly as many people as DCTG 23andMe have tested.

The real problem here: Pharmacogenomics tests are not something you hide, you ask your doctor to use these results. Unless you are a doctor, you can't use these results to dose medications.......

That is a real risk. Despite what WWDTCG proponents say.

Another risk, BRCA testing. I cringe at the thought that a doctor would use 23andMe results and only those results to infer carrier status of BRCA 1/2
The same goes for CF carrier status.

These DTCG medical tests aren't recreational. These companies added these tests because NO ONE wanted to pay hundreds, hell thousands of dollars to find out these risks.....

In a business decision, they fell short of looking at the medical risks.

So yes, a sliding scale of regulation is likely coming. But not because of Wylie, because of the FDA.

It is obvious. Again, medical testing will be regulated as medical. Ear Wax as ear wax. Will LDT be forced to go through pre-market review? Probably not if they can only be ordered by licensed professionals.....

It's not a form a rent seeking, it is a form of guidance and protection for consumers. That's why physicians are licensed and malpractice covered.

Yes, yes. Someday everyone will have these genomes done and everyone will be educated enough to know what they mean. And all humans will have medical education and we can replace the oligarchy of physicians and the tyrannical healthcare system once and for all........

But until that day, we will have to rely on trained professionals who don't have their retirements tied to their company's new genetic test......

The Sherpa Says: Handicapping of the FDA by the Sherpa. If it has any medical utility it will be regulated as either Class II or III. If only ordered via physician it will more likely be Class II. If not, will need Class III.

Kif 6, Genetic Findings = Useful Medicine 1 in 1000 times

2010-10-08T15:37:00.000-07:00

Way back in 2008 I mentioned an article, which I hoped would pan out. Or at least I hoped it would point the way to a model of PGx research which would be followed by pharma and alike to find associations to help us target the right medication for the right patient.

While the similar model followed through with Plavix, the initial study did not.

Which is why when the Berkeley Heart Lab guy came last week, I told him I would not be testing for Kif6. It had not been replicated in further GWAS.

Heck, I don't even use the 9p21.3 test......Why?

A VAP cholesterol panel, a HsCRP, a family history and a blood pressure can help me predict risk much better.

The problem and backlash facing DTCG and DTMD genetic test purveyors is

the 'Ol "Your million dollar major study now rushed to market has just been refuted"

Yes this happens in biomedical science and in medicine ALL THE TIME.

Bed rest for MI anyone?

Low Dose Dopamine?

I could go on and on, but I won't

Put simply, the majority of the genome is NOT ready for clinical medicine or clinical decision making.

It won't be for 20 years.

That doesn't mean there aren't some things we can use.

1. BRCA1/2

2. MMR genes

3. CYP2C19

4. CYP2D6, sometimes.....

5. SCD genes

6. Counsyl universal carrier screening

That is why the FDA is all hepped up about DTCG and even DTMD.

If a gene test comes to market that purports disease risk it had better be studied for at least 5 years before it comes to market.

Post market surveillance did not protect all those patients on Statins, "just because" of Kif6 risk.

Get it? These tests can lead to incorrect medical decisions....

Which can lead to risk.

Yes, even the DTCG tests can fool doctors and patients.

The Sherpa Says: If 2008 was the year of the GWAS, will 2011 be the year of the overturned GWAS?

A Whole Month Off, for Good Reason!

2010-10-06T18:44:00.000-07:00

I have a lot of friends and readers who have emailed me over the month.

The recurring comments: "Has the DTCG field run you off of your blog?"

The answer: "Uh No"

Why I have I stopped blogging so much? For multiple reasons.

1. DTCG has been put on the Radar of the FDA and Government. I have nothing more to say about that.
2. Journalists and Genomics aficionados have been correctly pointing out the hype behind some tests. Most notably lately with the ADHD stuff, which BTW should not have been put out there in the press....Maybe, I need to blog more.....
3. My practice and patients have really taken up my time. I am working to apply personalized medicine daily. Because that is what is needed. We need to show the public and the press how it is done on a daily basis.

I will be back soon, to dissect shotty science and poor clinical studies. But for now, our boots are on the ground and we are climbing the mountain....

See you soon!

Plavix and 2C19 BrewHahHah

2010-08-31T16:46:00.000-07:00

Yes,

I am a little slow

Yes,

It has been a long time.

But,

I am back. With a serious hankering to smash some studies. I already pooh pooh'd the Migraine SNP study on Twitter, but the Plavix stuff.....That deserves a blogpost.

To quote a famous caridologist and friend

"If Plavix really didn't work for 30% of patients, why don't we see more in-stent thrombosis?"

Translation: Your science is nice, but how does it fly in the real world?

I have to tell you, at first I couldn't answer. It was a great question. Do a full third of people have that severe failure?

The obvious answer is NO. If 1/3 rethrombosed, we wouldn't be using Drug Eluting Stents.

So what is the answer:

Apparently a BMS (I.E. Plavix maker) funded study investigated this

We hypothesized that the benefits of clopidogrel as compared with placebo would be decreased in persons who carry a loss-of-function CYP2C19 allele and increased in carriers of the gain-of-function *17 allele.

What did this team study?

we examined the efficacy and safety of clopidogrel as compared with placebo according to genotype status among patients in two randomized trials: the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial, in which patients with acute coronary syndromes were enrolled, and the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE) A, in which patients with atrial fibrillation were enrolled.

Ok, so they took 2 different populations and bundled them into the same article....

The 2 studies?

CURE-randomized, double-blind, placebo-controlled trial comparing clopidogrel (at a dose of 75 mg per day) with placebo — both in combination with aspirin — among 12,562 patients with acute coronary syndromes without ST-segment elevation.

ACTIVE A- was a randomized, double-blind trial comparing clopidogrel, at a dose of 75 mg per day, with placebo — both in combination with aspirin — for reducing the risk of stroke among patients with atrial fibrillation and at least one additional risk factor for stroke who were not eligible for warfarin therapy.

What did they find? No difference between Poor Metabolizer and Wild Type in secondary and primary outcomes.

So are we wrong with our studies showing 2C19 genotype matters in outcomes?

Probably not.

1st the authors note why.

1. One possible explanation for the divergence between our findings and those of previous studies involving patients with acute coronary syndromes is the difference in the rates of PCI with stenting. Only 18.0% of patients in the CURE population included in our study underwent PCI, and only 14.5% underwent PCI with placement of a stent, as compared with more than 70% in previous studies

2. We cannot definitely exclude the possibility of an interaction in the subgroup of patients who receive stents, particularly those who receive drug-eluting stents, which were not in use at the time of the CURE trial.

3. the ACTIVE A genetic data set contained fewer participants and outcome events than did the CURE data set and therefore had less statistical power.

My take

The ACTIVE A trial to assess the hypothesis was powered at 45% to detect a difference, thus it is a worthless study and should not be included in this analysis.

While I agree that a placebo group may be useful. It is not needed to assess a difference between people using Plavix with normal Plavix metabolism and Poor metabolism. In fact it may even confuse the situation as it introduces further confounding factors not genotyped or phenotyped out.

The authors disagree
First, the inclusion of a randomized placebo group in our analyses reduces various sources of confounding, such as potential pleiotropic genetic effects or population stratification.

Well, did they test or assess for pleiotropic genetic effects? No.

Further, by introducing a study COMPLETELY underpowered to observe and eval the hypothesis into this article, it ONLY creates a false image of scientific validity.

The authors disagree
Third, we observed consistent benefits of clopidogrel, irrespective of CYP2C19 genotype, in two different patient populations, which validates our findings and suggests that they could be generalizable to other populations.

Again to quote the article

Among patients with atrial fibrillation in ACTIVE A, our study had much lower power (45%) to detect a similar interaction.

So why did they include the POORLY POWERED study?

" in two different patient populations, which validates our findings and suggests that they could be generalizable to other populations."

While I laud the effort to have Randomized and Observational versus retrospective efforts. I think we have to be very careful in our study design to make sure

1. We are properly powered to observe differences.
2. That we assess pleoitropic effects, rather than claim to control for them mysteriously.

The Sherpa Says: Why include the second study? It is improperly powered, further the CURE study did not include Drug Eluting Stents! Why? Plavix goes generic in 2011. They did this to save the market......Expect more screwy studies published in NEJM etc. As PGx gains traction, contrarians and Pharm will always fight it.....

What is medical testing? Why it matters for DTCG survival.

2010-08-05T17:45:00.000-07:00

I just was threatened by Daniel MacArthur over at GenomesUnzipped that he was about to delete my comments.

He called it trivial. I think he is missing the tremendously simple point.

Why is the FDA mad as hell? Medical Claims.

Hell, they even told Mary Carmichael in the interview.

Alberto Gutierrez = AG

"AG: The concern is with everything."

"AG: The law requires us to clear devices or approve devices BEFORE they go into the marketplace when they make medical claims"

This to me is crystal clear. Make a medical claim. Get regulated.

Which is interesting. Because I would say some of what DTCG did was, infer medical claims without making outright claims- silly games . I happen to think that is a shitty way to sell something. But heck it is a way to create a discussion rather than instant regs.....

"AG: The question with 23andMe has been whether their claims were medical or not. The original claims they were making were very much on the edge."

"AG: We actually told them that WE(FDA) thought they were medical claims, but it was at least possible you could argue that they were not"

Do you get it? The judge thought they were medical claims, but let the company proceed. Giving it just enough rope to hang itself.......

The question here is clear. What is a medical claim?

Which boils down to: What is medical?

I can tell you what I do as a doctor.

I diagnose, treat, cure, palliate, prevent human suffering and advance human health.

If you are making claims to do any of those things, I would call it medicine.

This is very important to understand and I hope you VC are listening........

Diagnose, Treat, Cure, Palliate or Prevent human suffering.......and advance human health.

Words matter. Did you notice I didn't say disease. Because what's today's disease may not be tomorrow's.

And Vice Versa....

Is a priest a doctor? Well, they used to be.

Is a counselor practicing medicine, well, I would say yes, they are in the healthcare arena

Yes, it is now sinking in. That huge pit in your gut. The millions invested trying to game the system that is millenia old........

It will not work. DTCG has just proven that. And, do you think the vitamin industry has a chance over the next decade?

No.

I will begin the deep dive into the FDA comments shortly. But rest assured, I just gave you some insight into what medical really means......

The Sherpa Says: There Daniel, there you have it. I have told you what medicine is. Now if you wish to argue against that go ahead bub.......

Reporter Mary Carmichael, will she do it? Newsweek and DTC Genomics!

2010-08-03T07:16:00.000-07:00

" I don't even know if that was a hammer that got dropped on their heads. More like a piano."
-Anon Quote re: DTCG and Congressional hearings....

When Ms. Carmichael approached me to answer a burning question for her. She got an answer alright, more like a diatribe and then and answer.

In case you didn't know, Mary is a writer for Newsweek and is thinking about doing a DTC genetic test kit. In fact, she bought the kit and it is staring her in the face. FYI, she's not in New York, where such activity is illegal, she is in Boston, where it is encouraged......

She is taking opinions from just about everyone in the biz. And, yes, she has a comments section for all those Yahoos who feel left out.......

My recap here is what Newsweek wouldn't put in their print, but as you know.....I am more than happy to put here for my readers enjoyment......

Hi Mary,

You think you are set and ready to get, DTCG'd. Just hold on a second. I think you need to really think about what you can and can't learn from this sort of testing. Some say nothing, others say these little babies hold the secrets that the government is trying to keep from you, other say Google's overlords are plotting to steal your children's DNA.

I want to know, have you thought about it? What can you and what can't you learn? Since I have seen probably more patients with these types of tests than just about any clinician out there, I can tell you what the patients ask and what I tell them.

1. You will not learn what you will die from.

Yes, this is true. As a physician who has counseled and seen patients who have brought me their 23andMe, et.al., one thing is clear, patients ask about what this means they may die from.

This test won't tell you that, in fact most tests won't tell you that, whether ordered via Amazon or through your doctor. This test may show some scientifically linked risks for disease, but again, they won't tell you what you are going to die from.

As an aside, You will die from something. Everyone dies. Even those transhumanist singularity punks die. No amount of knock off stem cell clinics will help with that one. Even the G-Damn Buddha dies. In fact someone off'd him with rotten food....

2. You will not learn what diet is right for you.

Again, you are getting DTCG'd. But if you were getting some of the Nutrigenomics tests I would tell you the same thing, There is no magic diet currently based on 23andMe data or any other genetic data. We do know some people may benefit from some types of diets to lower cholesterol and lose weight, but the science to accurately predict genes and diet is not ready to bring to market, no matter what Proctor and Gamble tell you....

Second aside, Isn't funny how the GAO bashed these nutrigenomics companies in 2006 and they are still out there slinging there proton pills. Goes to show how much force the FDA or any other organization has to control commerce......I wonder what happens to the first batch who refuse to buy health insurance.....You can buy things that give you cancer or an erection, why not DTC tests? Properly regulated of course......

3. You will not learn if you are of the lost tribes of Israel.

True, your hot little hand will get a hold of a J Haplogroup analysis, but even the ancestry experts will tell you, this is a small window into heritage. Only 50% of the Cohanim have the Cohen Modal Haplotype. Is it a start? Yes, maybe a hint. But no SNP test offered by 23andMe will rule that out or in as J.E. Ekins et al stated. It requires extended STR testing.

Ok, my buddy, who shall remain nameless as he is at Camp in PA for his kids right now had a patient come to him adamant she was of the royal lineage of the Czar (Russia). She paid a bundle to have her mito DNA checked.....Guess what? She wasn't........

P.T. Barnum once said
"You can fool some of the people all of the time; you can fool all of the people some of the time, but you can never fool all of the people all of the time." But what he forgot to say is, some people are fools all of the time......

What will you learn?

Good Question Mary.

1. You may learn you are a carrier of a medically relevant condition.

For all intents and purposes, the lab used by 23andMe is CLIA certified, which means its results for positive carrier tests are just as valid as those ordered by a doctor (in some instances). But remember, this test is better at ruling in than ruling out as it often misses carriers in genes such as CFTR for cystic fibrosis. So if they say you are NOT a carrier, don't trust the results. And if it say you are you can always double check with a doctor.

Mary, this is a medical test. And should be held to the same standards as other medical tests.

2. You may learn you carry a rare mutation putting you at significant increased risk of breast or ovarian cancer.

23andMe tests for 3 mutations in BRCA1 and BRCA2 which could put your risk of breast cancer as high as 85% over your life. Are you ready for what to do with those results if you had them?

Mary, this is a medical tests and I advise you to have some clinician back up when reviewing these results. Even if they are negative, that doesn't rule out a BRCA mutation. This test is confusing and should be regulated as a medical test.

3. You may learn you cannot metabolize medications properly.

23andMe tests for medication metabolism using the same genetic markers as found in other medical tests. Again, they use a CLIA lab, so you may be able to trust their poor metabolizer status. But are you taking Plavix Mary? Tamoxifen? Does it really matter for you now? Or ever?

The whole thing about Pharmacogenomovigilence is that ideally everyone would have a panel of these useful genotypes before dosing medications. But based on the soon to be available rapid turn around time here, we could do these in some labs overnight. The big question here is, is the DTCG test enough of a test to trust clinically?

I am not so certain as they miss certain SNPs and rare mutations that are important.
The Sherpa Says: Ok, Mary. You want it, you got. If you buy a test, you've got a guy just a few Acela Stops away who can help sort out the madness for you.......Clinically of course.....That is, if I haven't convinced you otherwise.....

Another Ho Hum for SNPs, FGFR2 and breast cancer risk.

2010-07-29T06:09:00.000-07:00

The setting: Salvage of SNPs for Breast Cancer risk prediction published in JAMA yesterday.

The study: Women, 10306 with breast cancer mean age of Dx 58, 10393 sans breast cancer.

Outcomes:
1. Highest OR is 1.3 to predict Estrogen Receptor (ER) Positive vs ER negative with rs2981582 and 1.24 for rs3803662
2. The rest of the results were so suspect that the authors didn't include them in the abstract

"Certain Established risk factors for breast cancer have similar or even greater effects on breast cancer incidence that the differences seen here" -The Authors about this study's predictive model.

Bottom line: What good is a predictive SNP analysis of ER+ vs ER- if you can do that with pathology most of the time?

"Indeed or estimate of.....in the top fifth for polygenic risk score is similar to that for women in developed countries with one first degree relative with breast cancer" -The Authors about the less than useful polygenic risk model they created when compared to family history

Heck even the authors admit, this stuff is great......For studying pathogenesis, but NOT FOR CLINICAL USE TO GUIDE PREVENTION PROGRAMS!!!

The Sherpa Says: Again, "You would be in the high risk of pretty much getting it".........Not a good way to do medicine or guide consumers guys.....

FDA Tuesday, Congress TODAY. More letters for DTCG.

2010-07-22T05:30:00.000-07:00

I read with great interest Dan Vorhaus' post on the new letters sent to DTCG companies this week.

While it seems to me that these letters were probably planned beforehand, they may indeed be just trying to batch the "Publicized" I.E. Venture funded DTCG with the private funded DTCG. BEFORE, congress has a chance to sit down with the Big Money DTCG.....

I also disagree with his take that the FDA has worsened its position of trust with the LDT companies via these letters. In fact, what is going on as I speak with more LDT directors of labs, they are mad as hell. They are mad that these DTCG companies came in and screwed everything up in their nice little universe of LDT.

If anything, the FDA letters represent an effort to show clinically useful and ordered LDTs that they are siding with them and against the microcosm known as DTCG.

I think the Congressional Hearings on DTCG will prove the same here.

Back in 2007 when these companies launched, I expressed concern on my blog. I was concerned that these DTCG companies, which wanted to initially play down their clinical role, NITDOC loophole, would actually make the whole field look silly and create public distrust. I even predicted that this movement to "flip" a company I.E. "Create a revolution" may even lead to the death of personalized medicine

Unfortunately, that is exactly what has played out. At least the distrust part and definitely the confusion part. It appears the FDA is extending a lifeline to LDTs ordered by physicians and trying to amputate the DTCG arm of LDT.

LDT companies can either turn on the DTCG companies and devour them, thus saving themselves from onerous regulation or they can stay silent on DTCG at their own peril. This will be interesting to see how it all plays out.

One thing is for certain, what DTCG says or presents to congress will likely give lots of cannon fodder to the LDTs being used and ordered by clinicians and patients.....

Congress already has fodder to attack DTCG, they have been collecting it for a month. Wha? Those letters basically say "Give us everything. Tell us everything about how you funded and ran your companies. Tell us how you fixed your screw ups or didn't. We want it all. Emails, Texts, etc."

The Sherpa Says: This is not LDT vs FDA, this is Clinical LDT vs DTCG LDT vs FDA and The US Government. I think that if they fight it will be very ugly here. Congress needs to ask 1 question "Do you think you are doing medical testing? If not why not?"

Addendum: Video Sting from the GAO presented at the conference shows.

They are not only doing medical testing, they are giving medical advice.......

This industry is about to get blown up from the inside to protect the Clinically Useful and Valid labs. Those labs are about to feel the pain of a 2000 sample validation process......

FDA LDT meeting, bigger than just DTCG!

2010-07-19T18:34:00.000-07:00

At the FDA public hearing today, I began to hear a collective groan. The groan was from the LDT community that provide tests that are actually in clinical use today. You, see, this hearing is much more about LDT than it is about little 'Ol DTCG.

DTCG in fact was the perp walk that allowed LDT to now fall under question. For years, Home Brew labs up at Yale and Harvard and GeneDx and I could go on and on, went unscathed from FDA regs. Why? The tests were used by so few people and the case for harm was pretty weak.

Despite all of this, the FDA is now awoken and realizing it was asleep at the wheel here while the wagon train was being run by the Music Man! You can tell from the agenda that there is one thing at stake here........the future of nearly ALL genetic testing.

If you look at the list of speakers it was a hodgepodge of diagnostic labs, testing advocacy groups, consulting firms that bring biopharma through the pipeline and something called OMBU. WTF is OMBU?

Tomorrow is more of the same. Of course Wadsworth was there to represent some sanity in this process, thank god. But my big Gestalt from today's action is:

1. The FDA firnly believes it is time to get its act together in regulating genetic testing

2. The Genentech complaint from December 2008 really struck home with the FDA

3. The FDA regulates tests, not labs.

What does this mean.

Well I can tell you this. The FDA will regulate LDT and follow some line that it already has with things like AmpliChip.

I can also tell you, the LDT house is huge and a few little revolutionaries in DTCG have brought the entire house down. I am surprised that the genetic testing industry and academic labs didn't see this one coming. So many I know in the space were always pro DTCG, I warned them precisely against the regulatory scrutiny which LDT would face given "Oprah, Dr. Oz, Blimps, Open Bars and Trump"

They said, nawh, we are ok in this space and serve a need, why regulate us? I think in Genetech we just found the answer. How can we hold a corporation to a different standard than an academic lab? How can we hold a big company to a different standard from a small company? How can we justify that to the public? More importantly, to the court?

The answer: They can't.

The Sherpa Says: I don't think I could stand another moment of the FDA conference tomorrow. Instead I will play on loop C3PO saying "Please don't deactivate me"

FDA and the DTCG company MashUp.

2010-07-15T17:31:00.000-07:00

I know I said I would stop writing about 23andSerge. I will, but I am still going to write about what I think may go down next week in D.C. Land.

As you may know, I am a big supporter of classifying DTCG tests in certain ways

1. If the company has purported some sort of health benefits or decisions regarding medical care for a test, then it should be classified as a medical device and regulated as such. Class II or Class III

2. If a DTCG test does actually have medical implications for treatment, diagnosis or prevention, regardless of what a company says, this should be a Class III subject to premarket review.

3. If a DTCG test has nothing in the way of health implications or diagnosis, treatment or prevention it should not be considered medical.

If 3 should become item one or 2 based on new evidence, then it should be regulated as item one or 2.

What do I think should happen here with the FDA and DTCG? Well, it depends.

One has to ask first, will regulation stifle innovation?

If you ask me, most of this rhetoric is merely legal polemic. Very similar to how the Pharma companies complain about regulation. I have seen very scant evidence on the horrible effect it has on health or longevity.

In fact most of the "evidence" on regulation seem to come via law school papers and angry blog posts and twitter feeds.

But to get at the heart of this issue facing regulators we need to ask a follow up. Is innovation a good thing?

A priori I would say yes. Always? No.

I challenge anyone to prove to me that some innovation hasn't led to bad things or bad outcomes. "Magic Mineral" anyone? Or how about derivatives trading?

Assuming that not all innovation is good, we can see the role of regulation to prevent the harm of bad innovation. Is that such a bad thing? The general pubic doesn't think so. A poll in May finds that 72% of Americans trust the job the FDA does. They also are wayin favor of regulation of innovation in the space.

Now the FDA needs a litmus test for genomic innovation to define their regulation. What defines bad innovation?

I would say:

1. Potential for human harm from use of innovation.

2. Misrepresentations of expected outcomes from using innovation.

3. Lack of innovation performance of stated use.

I think in some ways, certain DTCG companies have had 2 and 3.

Number One is a potential in some peoples minds, but I have clinical examples that were presented by K.O. a year or 2 ago.

Unfortunately for the FDA, they have some lines and categories already which can create some rigidity in their guidance. And may not apply the scale I use.

But, it is just a construct. Similar to the one I presented before.

Will the FDA throw out traditional guidance here?

No.

They will follow the construct listed here, no matter how many people rant and rave at the DC meeting. Why?

I just told you. The public wants innovation in healthcare regulated. Which leads me to my next question. What do you think congress will do?

The Sherpa Says: We have to stop ranting about how the world will end if this tiny little field with the "unproven" ability to transform medicine sans clinician has to face regulatory scrutiny. Instead, we have to ask, is this a good innovation now? How will we make it a good innovation? Can we?

Longevity Gene Study, The hype cycle must die!

2010-07-05T17:57:00.000-07:00

You know what I love. I love a good story.

Magic research discovers Longevity genes, now humans live to 900. Just like Methusaleh.

Great headline. Unfortunately, this may not exactly turn out what it was cracked up to be.

From the WSJ 1 July 2010

"Scientists discover keys to long life"

"By analyzing the DNA of the world's oldest people.......They expect soon to offer a test...."

Tranlsation, here is why you should read this story about this amazing discovery, because soon you can take a test to discover if you will live a very, very long time.

Ok, this assumes

1. The study is correct
2. The statistics are correct
3. The findings are replicated

What's worse about the article is that there isn't even One Iota of, this is a preliminary and needs to be backed up.

Instead!

Instead, they say

"The free test will be available through a public website maintained by the New England Centenarian Study"

Come An' Get It!

Well, the website doesn't have the free test. But I bet it had a million hits the day the WSJ article and the press hype came out.

One may ask, as I am now, Once the afterglow fades, what will be of this test? Further, will the paper now stand the test of scientific scrutiny.

Just this week, despite the hype machine again rearing its ugly head like it did with Time's invention of the year in '08 or the blimps and Oprah. "An Age Old Problem Solved"? Really Globe and Mail?......We are met with discourse and doubt

There are some issues with the paper. Some skeptical about the effect size. Other's, like myself are skeptical because the SNP chip used for controls and cases was not EXACTLY the same. This can at times produce noise and false positive variants....

I am going to ask the hype machine again. Before running with an AMAZING Story, Mr. Hotz and everyone else in the press. Please take the time to get both sides and an analysis of the study BEFORE publishing the story.

The Sherpa Says: I hope this does pan out though, it sure would be interesting to have an estimate, in this case 77% accurate if you would live to 100. I use family history for this and it is not as accurate as 77%. Who gets that number anyways?

No more 23andMe blog posts. The Sherpa has achieved his goals.

2010-06-24T16:41:00.000-07:00

I am absolutely done talking about 23andMe.

Yes, you have heard correctly.

That doesn't mean I will stop watching what they are doing.

It means that I have coerced them into doing what's right. For now.

From the very beginning 23andMe had potential, heck Dr. Jeremiah Mahoney told me they came up to Yale to see them.

They must have not liked what Yale said, because they went further up the line and partnered with George Church.

Well, they def. didn't like what I had to say.

I had even conjectured about DTCG and what this landscape may look like and even warn about the shortcomings,
I had been pointing all of you to SACGHS to watch where this regulatory environment may go. The environment was heated with these companies going in.

So I knew I had to pay attention to what they were doing, especially the Google Backed company.....

First when these companies launch

1. I immediately point out 23andMe isn't using a CLIA certified lab which gives me grave concern over the seriousness with which they are doing testing. A-la Garage lab versus proper human sample processing.

2. I complain on Daniel MacArthur's blog about the obvious rookie blunder this company with no healthcare experience in leadership makes

Then 23andMe uses a CLIA certified lab

Second, I tell you that the states who have serious laws against DTC will shut down these companies quickly

Then they shut 'em down for a bit. And I gloat

Third

1. I complain that FDA needs to get their act together and in 2009 23andMe began doing absolute truly clinical testing with BRCA testing.

2. I point out the SACGHS feels the same way too and also complains to the FDA

3. I point out that 23andMe has no clinical clue what they are doing with PGx

Guess what? The FDA finally rules for regulation.

Lastly,

1. I complain about this research revolution akin to Tuskegee or other non IRB approved "research"

2. I point out that Google has off shore servers to hold this data free of US regulation.

3. I say that they are coercing subjects and offering discounts that wouldn't fly in an IRB

Today, they announce they have obtained IRB approval.

But I have my doubts as they have flaunted loopholes in laws And seem to point that out again today, or at least their blogger does.....

"our research technically does not require IRB review."

So I guess I will have to keep posting until these guys stop skirting lines..............Nevermind

The Sherpa Says: Yes, why keep it up if they did what I asked? Because they will do it again, even if it takes an act of Congress. Why do I ask? To protect the patient and consumer from mega corporations whose interest is anything but patient empowerment.

Ok, Spam Botted! Prasugrel PLUS 2C19 PM has better outcome.

2010-06-14T19:25:00.001-07:00

Alright, so I just found out that I posted a spam bot post. Not from a nice student named Ashley.

Instead what I will post is a subgroup analysis of TRITON TIMI 38. The subgroup analysis? 2C19 PMs and Prasugrel.

Great clinical question-Did the PMs (poor metabolizers) on Prasugrel fare better than the PMs on Plavix.

The obvious answer:
Duh, of course yes.

But Always we need some science and statistics here.

Individuals with a CYP2C19 reduced-metabolizer genotype were estimated to have a substantial reduction in the risk of the composite primary outcome (cardiovascular death, myocardial infarction or stroke) with prasugrel compared to clopidogrel (relative risk 0.57; 95% confidence interval [CI], 0.39 to 0.83).

Ok, so we should screen for PMs? Probably.

What about every other result?

What about the EMs?

For CYP2C19 extensive-metabolizers (EM) ( approximately 70% of the population), however, the composite outcome risks with prasugrel and clopidogrel were not substantially different (relative risk 0.98; 95% CI, 0.80 to 1.20).

The Sherpa Says: We should AT LEAST be identifying the PMs and placing them on Prasugrel. This subgroup analysis shows increased risk while on Plavix. Primum Non Nocere.

Answer to GenomicsLawyer's Question. What the FDA will do with DTCG.

2010-06-12T04:32:00.000-07:00

Dan Vorhaus JD on his blog says "The path of least resistance may be to simply agree with the FDA....The viability will depend on how the FDA intends to categorize the specific product...."

I agree, these companies have big choices to make. If it is any indication, Counsyl (full of smart people) and now, Pathway Genomics (full of smart people) have both decided to go the route of Medical test.

Perhaps it is because they think the burden will cost less to investors than fighting the "Man"

Well, in guessing what the FDA will do, it is always best to see what they have done to a "similar" product. In this case, they have a great product that is very similar. That would be the FDA's approval of AmpliChip.

A friend of mine in Canada argues about the holes in this platform, but unfortunately it is the only FDA approved platform.

You can read the letter for the FDA approval here

This was cleared in 2005! I wonder if the DTCG companies ever looked at AmpliChip as a model before?

In the letter it is clear, microarray technology used for drug metabolism prediction is considered a Class II medical device. The letter indicated that this applied not only to AmpliChip, but also to similar devices.

It also does not waive premarket submission.

Both of these are very important points in how the DTCG groups evaluate their future business models and potential market.

The Sherpa Says: Why Conjecture? Just look at what the FDA decided for AmpliChip. It will be a similar template.

I am glad we can all put this behind us. FDA rules on DTCG.

2010-06-11T10:46:00.000-07:00

As you now may be aware. DTCG is considered a medical diagnostic according to the FDA. I look forward working with companies who may now allow me to use their tests for medicine.

The Sherpa Says: If we work together, we can deliver the best preventative and personalized care in the world!

Cellulite On Your Bod? Blame your genes! Or market 'em!

2010-06-10T18:26:00.000-07:00

Could I go on a huge rant about 23andMes mess up and how it was discovered by a customer rather than LabCorp or 23andMe?

Yes. Would it be useful?

No.

Why?

I need to save my rants, and any doctor will tell you, labs screw up all the time.
It is something we are used to thinking.

So much so, that a knee jerk answer for a lot of doctors is to repeat a test if the results are so far out there.......

So, my rant today will be directly placed at the rocket scientists who dreamed up CelluliteDX

"The CelluliteDX Genetic Test is only available for sale through participating physicians' offices. If you would like to learn more about the CelluliteDX Genetic Test and receive a Welcome Package to establish your office as a CelluliteDX Genetic Test provider, please contact us Monday through Friday between 8 a.m. and 5 p.m. Pacific Standard Time or e-mail anytime"

Ok, this is the problem that the DTCG community has and I do too.

Doctors may be using crappy tests as a marketing ploy to drive patients through the door. Well, some DTCG does market crappy tests to drive customers through their portal too. But this one takes the freaking cake.....today

This test which BTW is the ACE genetic variant testing has a full page called "Science" where you can read about this brain trust.

200 patients, 200 controls, the offering......

"A physician using the CelluliteDX Genetic Test for Moderate to Severe Cellulite, can predict that a patient who tests positive has approximately a 70% chance of developing Nurnberger-Muller grade 2 (or greater) cellulite."

The science: Is there a paper on this? Seriously? A gene for cottage cheese butt? Awesome! You've gotta love Italians and there passion for the A$$

"the multivariable-adjusted odds ratios for cellulite were 1.19 (95% CI: 1.10-1.51; P <> 1.19 huh?

How is that 70% increased risk? Would love to see that please. No, seriously, tell me how. This is why Congress jumped. What Doctor in their right mind would offer this test?

The Sherpa Says: This is why we need education of physicians and the public here. Hullo? FDA, maybe they should get a letter too?

DTC Genomics adjusts for regulations. 23andCGC?

2010-06-04T15:26:00.000-07:00

In a blatantly obvious, why the hell werent they doing that in the first place? move.

23andSerge acknolwedges, finally, that they ARE Providing clinically important work. Duh,

Since the website won't let me copy the presser, I will quote, with my own translation through business BS speak.

"23andMe customers now have the option to speak with a board certified genetic counselor"

-Translation, we realized that by testing BRCA mutations we put people at risk and needed some back up from someone who knows what the FCUK they are doing opposed to a VC billionaire babe and ruby on rails programmer kids.

-Because, frankly, we don't want to get sued or go to jail......Like Liz Dragon......

"We chose Informed because they were the leading independent genetic counseling provider"

-Translation, we alienated/pissed off the entire rest of the FCUKING community by saying they were stupid. Thus these were the only guys who would work with a company getting ready to be pilloried by Congress

IMHO, Informed are a great service, we are modeling genetichub after them, but... No one else would work with them on this. NO ONE, or so I am told......

"We wanted to be sure that the information our customers receive would be completely objective"

-Translation: We didn't want to have egg on our face when the geneticists said, "Well Andre, that finding essentially means nothing to your long term health and happiness"

"Customers who want a more thorough review of their family and medical histories can chose the Comprehensive Clinical Genetic Counseling"

-Translation: Yes we know we have been pushing this "It's not clinical" thing, but let's face it, no one is buying it. So we said Clinical, yes we did. See Henry, we are trying Congressman. See. Please no pre-market review.

The Sherpa Says: Well 23andMe, I am proud you came around. Too bad it only took an FDA review and being called to testify before congress before you "acted" in the best interests of your customers. 3 years later and I can say it. I told you so......

5 Days after the Quake Critique

2010-06-01T08:15:00.000-07:00

I want to know, when everyone got all upset with my review of the Quake paper and bashed me on this blog. Why?

Why did no one post on the Viewpoint put out in The Lancet exactly 5 days after my review?

What did my review say? You can read my analysis of the Quake Paper here.

I will keep this brief, as I will be speaking precisely on this topic on Thursday at the Consumer Genomics Conference.

Maybe no one read the viewpoint?

Today I was able to read the

"Challenges in the clinical application of whole genome sequencing" Viewpoint from Ormond et.al.

It echoes every single thing I have been saying for the last 2 years. Not that any of this is news for those of us in "the know" But it is confirmation that people who include a DIRECT Advisor to 23andMe agree with my stance.

However, there are some things in the paper that I disagree with.

1. "The author assumes that because of the rapidity of cost decline with WGS (whole genome sequencing), that it will be used more and more in Medicine."

I disagree.

Payors, Clinical validity and Exposure to malpractice risk will determine the uptake in the clinic

2. "Reduced sequencing costs seem likely to cause a rise in WGS"

I disagree.

Perhaps in research this will be the case, but for customers, who are now staring down the barrel of an FDA investigation, House of Reps investigation, they may think twice. No matter what Oprah has to say.

3. "even if that information averaged only 3 min per disorder, this process would take more than 5 hours of direct patient contact, after many hours of background research"

I disagree.

The average time per disorder would be at least twice that, meaning ten hours of direct patient care. Which on my clock is about 4000 USD, at least.

4. "As academics, we often assume that information is good and more information is better. but more information can sometimes be counterproductive"

I agree whole heartedly.

I know many excellent academicians who say "Garbage in, Garbage out" or "Information is just that, but Noise is Garbage"

The Sherpa Says: We need to bite things off a piece at a time. That is the problem with whole genomes. People will need to be revealed information in a staged fashion WITH SKILLED CLINICIANS. Nice to see Russ B Altman MD et.al., advisor to 23andMe agree with what I have been saying over the last 3 years now.

Breaking 23andMe's Terms of Service: Not just the patient's problem.

2010-05-26T06:49:00.000-07:00

A blogger over at 5Am Solutions Blog is about to break 23andMe's Terms of Service.

"So I called my primary care physician's office and told the appointment-taker I wanted to discuss my 23andMe results with my doctor. She said 'ok' and scheduled an appointment for next week."

May I just add. It is not the doctor breaking the Terms of Service here. It is the customer by bringing it in to their doctor.

From Andrew Yates Blog at ThinkGene

"BOOM! That patient coerced that doctor into malpractice liability.Section 3 of 23andMe Terms of Service: “The Services Content is not to be used, and is not intended to be used, by you or any other person to diagnose, cure, treat, mitigate, or prevent a disease or other impairment or condition, or to ascertain your health.”

The worst of this is that 23andMe ACTIVELY INSTRUCTS its users to violate this clause —not only personally, but to also implicate their medical doctors in crime.

And the doctor is trapped: he can respect the law and alienate the patient, or ignore the law and appease the patient."

Oh, wait. Maybe by using 23andMe I am now involved in their legal mess? Crap!

That being said, I just received the Counsyl results from one of my patients yesterday. Unlike being put in a risky position by the good folks at 23andMe, Counsyl is straight up clinical and useful.

I will be notifying the patient via secure email of his results and spending an hour going over it with him.

The Sherpa Says: 23andMe, just like others in the space have demonstrated a general disrespect of the precarious position they have put physicians in by using such crazy and convoluted Terms of Service to avoid regulations. But heck, why should they care about the hot water they put us in.

DTC Genomics reviewed in Genetics in Medicine

2010-05-24T05:11:00.000-07:00

I just received the May issue of Genetics in Medicine, only 24 days late. But it caught my attention for several reasons.

1. The issue is covering Adult Topics almost exclusively this month

2. They review the Multigenic risk assessment in DTCG

Granted this article was a single author MBA, it was notable at the work she must have put in to this review.

Methods:

1st she did an extensive analysis of the service 23andMe, Navigenics, deCodeMe, Gene Essence. She assembled the 20 multigenically evaluated conditions, reviewed website data, and deep dove into the studies, average pop lifetime risk, loci, genes, SNPs, Quant risk assessment, and methodologies.

That sounds very similar to what the FDA is requesting to do. In their case with non publically available data as well.

2nd she did a complete locus analysis which is available here.

Results

Analysis 1.

213 conditions covered by DTCG companies, with only 9 conditions covered by all identified companies. 15 addition covered by 4/5 companies.

Analysis 2:

Lifetime average risk values of the same populations.

It turns out that the companies provide different life time risks for the same disease in the same populations.

This is not a big deal to me if you wiggle 2-4 points. But some vary widely

Glaucoma 1% in Navigenics while it is 15 for deCodeme

Heart attack 42% for Navigenics and 21% for 23andMe in Men

Heart attack in women 25% in Navigenics while it is 7% at 23andMe

DVT 3 percent for Navigenics 12% for 23andMe

23andMe does not provide references for their lifetime risk data.

Heterogeneous SNPs and Loci Assessed

No big surprise here, it turns out each company has their own way to make a Big Mac, each has their own special sauce and pickles/onions and even their own sesame seed bun. Thus you get different SNP risks given to customers.

A total of 224 loci are covered 401 SNPs for the 20 multigenic conditions. Of the 224 loci, 115 are only covered by one company. 63 are reviewed by only 2 companies.

For 12 conditions covered by all 4 companies, only 9 SNPs were covered by all. These 9 SNPs represent ONLY 3% of the total SNPs covered by all 4 companies and 18% of all loci covered.

Heterogeneous quantitative risk assessment

Once again, different risk assessment methods rule the day at these companies. Just like if I were to use Reynold Risk instead of Framingham risk but at least I have some data to base my conclusion. We have none of that with the DTC company risk models......

On Saturday I had a pissing contest with Thomas Goetz of Wired Magazine and his book called The Decision Tree,

He kept saying, It's My data. I kept saying. Fine, but the interpretation needs to be regulated.

I think we have a very decent reason why right here.

When you get a cholesterol of a blood pressure reading in the United States, you would hope the interpretation you receive is standardized in some way.

Further you hope at least the person giving you the interpretation of that data has some sort of licensing to assure quality and accuracy.

Unfortunately in this field there are many, many unknowns. This makes the risk prediction even less accurate. So it is no surprise these companies have widely variable assessments. But what does trouble me more, is the fact that they seem to not have done their homework with average lifetime risk populations.

That seems like they should be at least on the same page with this information. And why 23andMe has not listed reference articles for their quoted population risk is beyond me.

The Sherpa Says: Doctors go to medical school for 4 years, then go onto residency for 4-8 years and some do fellowship for another 2-5 years. And then we give risk assessment and diagnose and treat. Why do people forget that? Oh and we first operate under the principle of First Do No Harm. What doesn't Mr Goetz get about that?

Thomas Goetz has the wrong debate. FDA doesn't intend to restrict.

2010-05-22T11:49:00.000-07:00

I think everyone in this space has been way off base as to what the problem is with FDA and Congress wanting to investigate the DTC Genomics companies.

The whole mindset is wrong.

What I hear from this debate is "It's my data, mine, mine, mine. Gimmee, Gimmee, you can't keep me from my data Big Brother!"

From Mr Goetz's Blog
"The controversy seems to have stirred the FDA to assert its authority – and that of physicians – over any and all medical metrics."

"To me, getting access to this information is a civil rights issue. It’s our data."

This is a straw man argument that has been set up to make regulating these companies seem unseemly and an invasion of privacy.

IT IS A DEAD WRONG ARGUMENT and I will not stand for it being perpetuated anymore.

This is not about getting access to your data.

Fine, you want a whole genome, go get it!

The FDA is not asking should people be able to go out and buy this. It is asking several other questions.

1. Is Interpretation of biometric data considered medicine?
The answer here is certainly confusing. I think it rests solely with intent.
Do you intend to tell someone something about a disease they now have based on this biometric data that you analyzed?

If the answer is yes, that is viewed legally and medically as a diagnosis.
Which ultimately I think is medicine and falls under medical regulations.

2. Is DTCG analyzing biometric data and intending to give an interpretation of that data which indicates a disease a person has?

It depends on what you define disease as.

Most legal experts defer to the International Classification of Diseases

3. Should we regulate a system which has not given indication of their quality control if they are indeed intending to provide medical diagnosis?

4. Are these methods of obtaining human samples to derive biometric data for the intent of analyzing and providing information about disease considered medical devices?

This is precisely the argument and precisely what Congress and the FDA are trying to define.

So stop acting like a bunch of little kids running around because someone took your kool aid away!

If I hear another, "It's my data" whine again I will scream.

This is not about restricting access to biometric data.

Which by the way, some states do already.

Is an EKG biometric data? What about a cholesterol?

Probably, no one is stopping you from going out and buying a machine to obtain this data yourself.

But any doctor will tell you, it is the interpretation that can vary widely. As demonstrated by the multiple interpretations that Venter et.al complained about

What they are intending to do is to prevent a third party from having NO ONE to answer to when providing interpretation of that very SAME biometric data.

The Sherpa Says: Regulation here will most definitely not stifle innovation as bad as a consumer death or class action lawsuit or lack of trust from consumers because of the aforementioned.

How Bad Can a House Investigation be for DTC Genomics?

2010-05-20T05:16:00.001-07:00

Ok, so you've been summoned to Congress to testify

It won't be that bad if you know what you are in for. So let's review.

1. A chart listing the conditions, diseases, consumer drug responses, and adverse reactions for which you test;

2. All policy documents, training materials, or written guidance materials regarding genetic counseling and physician consultations, including documents regarding what conditions, diseases, drug responses, or adverse reactions trigger the need for genetic counseling or physician consultation, and documents governing communications with consumers regarding individual genetic testing results;

3. All documents relating to the ability of your genetic testing products to accurately identify consumer risk, including:

a. internal and external communications regarding the accuracy of your testing;

b. documents describing how your analysis of individual test results controls for scientific factors such as age, race, gender, and geographic location;

c. third party communications validating the association between the scientific data your company uses for analyzing test results and the consumer's risk for each condition, disease, drug response, or adverse reaction as identified by the results of an individual test; and

d. documents relating to proficiency testing conducted by your clinical laboratories.

4. All documents regarding your policies for processing and use of individual DNA samples collected from consumers, including:

a. policy documents and protocols regarding collection, storage, and processing of individual DNA samples;

b. policy documents and protocols relating to protection of consumer privacy; and

c. documents regarding collected DNA sample uses other than to provide individual genetic counseling to a consumer, including documents relating to third-party use of collected DNA samples.

5. All documents regarding compliance with the Federal Food, Drug, and Cosmetic Act and

U.S. Food and Drug Administration (FDA) regulations.

And you should have that to them in about 2 weeks.

What could be so harmful?

If you know anything about the history of such investigations, they are mostly a dog and pony show that ends up in one of a few options.

1. Public Pillorying that leads to a slap on the wrist and a consumer base who doesn't trust you anymore (See Toyota)

2. A massive class action lawsuit from some enterprising attorneys who review the publicly available documents that the House requests via Freedom of Information.

3. The Congress forces you to behave like normal society rather than a bunch of radicals trying to take over the world.

4. Some clone company sees all your internal documents via a Freedom of Information Act, copies the good, removes the bad and launches in like 6 months.......

5. Someone goes to jail, perp-walk style.

Since 5 is not realistic, I think we can expect some combination of 1-4 for these companies.

The worst outcome is probably Number One here.

The consumer base already doesn't trust Google/23andSerge

Navigenics already has a distribution network, but if the physicians don't trust the test, they won't order it.

Pathway will have a bump in the road and no retail launch.

Number 2 could hurt too, especially Ms Wojiciki who could get personally named in the suit as well as investors like Dyson.

If I was the lawyer, those are the deep pockets I would be after. Navigenics is owned by P&G now and their corporate counsel will likely shield them.

Pathway has probably the least customers to be exposed to such a lawsuit, unlike 23andSerge's 30k

Number 3 stinks for the "Research Revolution, Che Style" but probably won't hurt Navigenics or Pathway.

Number 4 is a definite reality. I have already heard that scuttlebutt on the street.

So, I ask. Is getting companies to behave responsibly and acknowledge that some of what they are doing is medical testing so bad? Ryan made the move. Very smartly Ms. Phelan. I knew she would.

The Sherpa Says: This certainly is a nice distraction from Tar Balls and Toyota...

Couldn't you have picked a better Gene Set Berkeley?

2010-05-19T05:49:00.001-07:00

I admire UC Berkeley for pushing the envelope. They have been doing it for decades. Encouraging risk taking, and defying stereotypes

But when I read about their summer research project I cringed.

We are going to test students' ADH and tell them whether or not they can process alcohol properly.......

Excuse me?

Ok, I get it, poor metabolizers will cut down on drinking so much, The UC saves on risk management insurance, win for the administration and win for the educators who will then "teach" about the findings......

What about that party-hardy freshman who has that timid roommate? well, the roommate just found out that she can process alcohol "just fine"

@KTVU news at 11. UC Berkeley student found dead after party.

"Well, it all started when she found her genetic test results meant that she could handle alcohol just as well as I could"-Dead Student's Roommate

Couldn't they have picked a better gene?

What were they thinking? I dunno, maybe they were blinded by Time Magazine. Well, the good news is that all Berkeley Freshman will all be entered in a drawing to receive a free test from, Guess Who?

23andSerge

The Sherpa Says: First Do No Harm

Potential of genomic medicine, LOST

2010-05-17T07:11:00.000-07:00

I was reading and often read Mark Henderson of the Times

The piece I just read about the "Potential of genomic medicine could be lost, say science think-tanks"

The piece basically comes down to one conclusion.

We have no proof that most of this stuff is useful in any form.

This is something that I have been shouting from the roof tops ever since some self deluded socialite from Mountain View decided to say "Genetic testing is for fun"

Seriously DTCG. You knew this day was coming. You tried to play yourself off as hip, cool, sexy/ Yet at the same time to avoid regulation you played, not serious, not clinical, and in essence, not valuable.

I was deeply concerned about precisely this issue. By putting yourselves out there as an invalid in the clinical world, you cheapened the field and some of the tests that you offered.

Because of this conglomeration of useless with useful, the field of medicine and healthcare as a whole needs to create systems to sift between marketing and PR spin/hype from truth and medical utility.

Luckily in the US we have such a system EGAPP. We also have things such as the CPMC ICOB. But in England, they have no such official system.

What is even more troublesome is the lack of clinical utility of such tests and lack of funding to evaluate the utility. The problem with this rush to market the next GWAS is emblematic of this over hype cycle that exists in medical science.

Why?

Medical scientific discovery can or cannot be useful in medicine.

That is all.

Saying something promotes "Health" rather than treats,cures, prevents or diagnoses disease to avoid regulation confuses the public and unsophisticated venture capital. Which really makes me wonder if that is what you had intended in the first place........

What should have been said is "These tests have not been proven to prevent/diagnose/treat disease nor have they been proven to aid in healthcare"

But that probably wouldn't have sold many kits......Thus the problem with medicine, you can't just "fake it" with Time Magazine.......

What your "faking it" has done is created a hornets nest on both sides of the pond with governments scrambling to decide what matters.

"Caroline Wright, head of science at the PHG Foundation, said: “The heart of the problem is that we do not have enough data on whether these tests actually help patient care. We desperately need the equivalent of clinical trials for diagnostics."

Further, the UK doesn't have a team equivalent to EGAPP over here. Which BTW, K.O. if you are listening, I would love to be a part of..."I'm just saying......"

We need to ask ourselves as Andrew Yates points out, what results can we expect when the average death percentage over time in this country or any others is 100%

Will a flashy test keep you alive longer? Not if it has no clinical data proving that it does.

No amount of blimps and SoHo parties will prevent death or disease. Sorry.

The Sherpa Says: The Quake paper was their best shot of integrating this into clinical care and they are arguing about whether or not to put him on a prophylactic statin? Which BTW has no evidence behind it........Personally I think that shot was misfired......

GateKeeper? F! U!

2010-05-11T17:41:00.000-07:00

Dan Vorhaus recently had a great post about the FDA coming in to carpet bomb DTC now OTCGenomics.

But what I am pissed off about is everyone using the term gatekeeper connoting a doctor required to do something.

What the FCUK do you think I am? A gatekeeper is a lot like a door man.

I don't get your bags.

I don't just open the door for you.

I am not profiting from the test that is ordered.

I am saving your f'ing life.

Stop calling me GateKeeper and call me what I am.

Doctor. Sworn to save your life.

Last post edited by Drew

2010-05-11T08:18:00.001-07:00

"Clinical Assessment Incorporating A Personal Genome"

The clinical assessment was incomplete.

It was missing the following items

1. A Physical Exam
2. A Complete Pedigree with ethnicity
3. Appropriate Clinical Laboratory testing
4. A Full Social History

Grade?

D minus.

Adjusted for curve a good solid B minus

But ultimately, this novel approach is clinically unfeasible.

Why?

The manpower alone required to perform this "clinical" analysis is unsustainable for 300 Million people.

Personal Genomes in Clinical Care. Quake paper Falls Short!

2010-05-10T17:34:00.000-07:00

With all due respect to the scientists involved in analyzing Stephen Quake's genome in clinical context.

You did a major league $h!tty job.

No offense.

I can only assume this based on what you reported in the lancet paper.

Start by asking yourself.

"Is Stephen healthier because of what that genome and clinical assessment added to his care?"

I am speaking precisely on this topic at the Consumer Genomics Conference on June 3rd at 830 AM. So I will hold off on all my arguments....But,

The Paper even says

"We noted that most of the sequence information is difficult to interpret, and discussed error rates"

Ummm, ok. Nice counseling session.

"patients with whole genome sequence data need information about more diseases with a wide clinical range"

Perhaps that person could actually be a physician, maybe a generalist?

"For this we offered extended access to clinical geneticists, genetic counsellors and clinical lab directors"

Nice! Joubert's is not Gilbert's is not Plavix. Thanks for stopping by.

I did appreciate that your paper calculated pretest probabilities. Unfortunately these were based on a pedigree which had no ethnicity and incomplete clinical data.

1. No Glycohemoglobin to evaluate for diabetes risk or maybe even diagnose it
2. No Iron Studies to evaluate for Hemochromatosis, yet you state genes may set him up for it.
3. No documentation of a physical exam including DRE for prostate hypertrophy/cancer or PSA
4. No dietary history? No Smoking history? No social history?

Shall I go on?

You show increased risk for Diabetes post test as well as prostate cancer, obesity, CAD, MI, Asthma, NHL, RA (no ESR/CRP/CCP?)

You projected an increased risk for 7 and decreased for 8. Yet no Assessment of MCI etc in Alzhemiers disease? My god, you did a stress test in an asymptomatic patient who exercises daily.

"Although the methods we used are nascent, the results provide proof of principle that clinically meaningful information can be derived about disease and response to drugs in patients with whole genome sequence data"

Translated: We made up a system and used novel DNA results to hypothesize about disease risk using research fellows, computer programs an excellent cardiologist (Not a GP) and an Echo machine.......But we skimped on the physical exam, use of primary care doctors, complete blood counts and other clinically useful testing and procedures.

I admire your efforts, but

A. You have missed the boat in using not all the tools at hand
B. By being Genome-centric, we miss the clinical picture.

"Although no methods exist for statistical integration of such conditionally dependent risks, interpretation in the context of the causal circuit diagram allows assessment of the combined effect of environmental and genetic risk for EVERY individual"

Translation: Nothing exists statistically to evaluate disease interaction and how it may increase risks of interlinked disease.

Ask yourself, "What have we done to make Stephen Quake healthier from this test?". Other than hype the use of a genome clinically?

This paper was all genome and NO CLINICAL ASSESSMENT!

The Sherpa Says: The only thing of note that is important here is the CYP2C19 data.......
I have seen abnormal CGH data in a child with severe developmental delay come directly from a high functioning mother who was a power litigator. The genome scan as it stands now is noise. It also requires a full team a month to intepret. Clearly not ready for medical prevention or prognostication, sorry.

Coriell Personalized Medicine Collaborative rising

2010-05-06T18:30:00.000-07:00

This evening I want to write about something amazing I recently was able to participate in. It was the first meeting of the Pharmacogenomics Advisory Group. This group, chaired by Issam Zineh is pretty amazing. Let me tell you why.

1. Members of PAG have been involved in pharmacogenomic studies involving most if not all current markers
2. They include members/contributors of PharmGKB, FDA, AAPS award winners, Howard MacLeod, I could go on and on.....and one lowly blogger and clinical personalized medicine specialist.....
3. The group was willing to engage in active criticism of each other and of ideas. That is the key to a great advisory group.

While we see the dropping costs of genotyping going further and further with some quoting a 10k genome by June's end, it is becoming crystal clear that the test is not the product. The test is a razor handle. Seriously. It will be given away free. But the question is, what will we do with it.

Coriell is aiming to answer some of these questions and is engaging in ethical research. Coriell is the cohort study that we will turn as we turn to Framingham. When the next decade closes we will sit back and laugh at how all of the VCs dumped money into supposed 1000 gene tests that gave nearly useless results or results that couldn't be used for what they needed to be used for by Terms of Service......

At the same time, we will see how a sleepy little institution in Camden NJ, known for holding cells became a powerhouse in the Personalized Medicine Movement by holding patient lives and medical data......with a little help from their friends........

The Sherpa Says: If you haven't joined the CPMC, you should. They are climbing the mountain skillfully

2C19, Navigenics and Clinical Reality.

2010-04-29T05:28:00.000-07:00

Ok,

I would like to welcome Navigenics to the world of Clinical Utility. Just yesterday they announced their pharmacogenomics panel available to both consumers and physicians. It is about time!

However, the problem I see is threefold:

1. Where is the price of the test? Anything more than 200 won't work.

2. Is there a change in the terms of service, which allows me as the doctor to use it?

3. Will insurance pay for it?

Let's say that this is not intended for the doctor but instead just for the patient/consumer. Which Navigenics has agreed NOT To Do, At least in NY.

What exactly do you expect the consumer to do with this information?? Stop Plavix? Don't you Dare!

Write themselves a prescription? Ummmmm, OK.

Oh No, these tests are specifically for medical use.

Disagree? Merely the information itself is important? What good is information without ability to act on it? maybe you should ask Cassandra?

There are multiple companies out there offering PGX testing in one form or another. This makes the following questions of utmost importance

1. Which SNPs are tested?

2. Can you really trust a genetic counselor to give you advice on medications? How many have they prescribed? No offense, just reality.

3. Will the laboratory results and work in a clinical setting, integrated with clinical care?

Just because you're a great product backed by venture capital, with with analytical validity and the plan to get to market doesn't mean you will succeed in the market. Why? Most consumers still trust genetic testing decisions to be made by the doctors.

How do I know this? I'm the doctor. I am licensed to give clinical advice.

The Sherpa says: Why these DTC companies try to cut out the doctor is beyond me.

99 USD, DNA day and patient letters

2010-04-23T08:29:00.000-07:00

Yes,

What a great DNA Day!

Today started with my twitter feed notifying me that 23andMe had dropped their prices to 99 USD today. Which almost had me encouraging people to get testing, until I remembered that 23andSerge would then have your DNA..........FOREVER!

Then I opened my email and read this great note

"Dear Dr. Murphy,

Thank you so very much. I am so lucky to have found your team. Who would have thought my Plavix might not be working for me? Only when you told me about how it could not work did I realize that I might be taking something that is worthless. Thanks for testing me. Now that I am on Effient I feel much safer!

Thank you Dr. Murphy,

You saved my life!"

That's right. A genetic test, may have saved this patient from a heart attack. A genetic test I do regularly. Who has this patient's test result? Not some corporation that will use it for profit. No, just me, who will use it to act medically. While as these other services say explicitly, YOU CANNOT USE IT FOR MEDICINE!!

To be certain, you should not stop your Plavix WITHOUT talking to your doctor first!

Shame on them, their test could save a life. But not according to their TOS.

I will be speaking at the Consumer Genetic Show about precisely this problem and others. I was so surprised that they asked me to speak. Especially after the beating I gave it last year.

But on this DNA Day I am here to tell you, the public is aware now. DNA testing does hold promise, but only when in the right hands.........

The Sherpa Says: Pharmacogenomic testing IS MEDICINE. It is NOT FOR $H!T$ AND GIGGLES! Happy DNA Day!

Happy DNA Day!

2010-04-23T06:34:00.000-07:00

As I send off my third genetic test today in my Personalized Medicine Practice I want to wish everyone a happy DNA Day!

More to follow. I promise!

The Rumors of My Death........

2010-04-20T05:14:00.000-07:00

You know how the rest of the story goes.

Frankly, I have been running flat out for the last 6 months. I have been working with some amazing computer scientists, lab specialists, geneticists and physicians putting together some "side projects" while seeing patients on a daily basis for "Personalized Medicine"

The practice is busting at the seams and we are pretty excited about the next few phases of growth.

I want to share with you some news.

1. Yes we have iPads and are using them for rounds, patient registration and education. Soon we will have our own private apps too.

2. Out of the bundles of CYP 2C19 patients we have been testing we have changed more patients to Effient than I can count. Saving lives along the way.....

3. Yes, the rumors are true, I will be speaking at The Consumer Genetics Conference in June! Along with pound for pound the best MD CEO around Brandon Colby, who must be coming out of stealth!

I will post more soon, but rest assured, I have a huge team climbing the mountain with me.

What did I do? Well, I didn't get them drunk at open bars. Nor did I woo them with money.

I did the heavy lifting that it takes to put "Theory" into practice. If you want to see how, stop by

Greenwich or Stamford.......or better yet, make an appointment 9hh@hhdocs.com

The Sherpa Says: Stay tuned

Sherpa Accepting Chief Medical Officership

2010-04-01T03:50:00.000-07:00

Now that it has been announced in China. I am proud to say I will be accepting the Chief Medical Officership for Baidu's new Whole Genome Sequencing service called XY or Die.

This is an exciting time for this field and I have to tell you, despite my displeasure with some shady DTCG marketing practices, I feel Baidu's strategy of feeding ads based on genome information could prove to "empower" patients helping them purchase just the right set of herbs and melamine laced baby formula to ensure the best outcomes for the patient and their potential offspring's IQ.

Yes, it is true. I have often been critical of these obscene flagrant violations of United States Law, but in the Far East, there are no laws here.

So, when they come at you with a few million, why not take the money and run?

Sorry, I meant, how dare those repressive capitalist pigs stifle innovation and patient empowerment?

Further, their movement to resemble medical technology and with a wink wink and nod nod insinuate that they are doing medicine, without the doctors. Really, who does need those over paid, money grubbing arrogant assholes anyways? They often end up just looking to churn you for money.....

The Sherpa Says: April Fools, Get a grip!

End of Gene Patents?

2010-03-29T16:44:00.000-07:00

With the NY district court ruling in ACLU et.al. v USPTO/MYGN it appears clear that the bar for gene patents is super high and most will likely not reach it. Does this mean the end of gene patents or even just the BRCA1/2 patents?

No, but it is the beginning of slipshod sequencing and a whole host of labs testing for BRCA1/2 sequences. It is also the making of a SCOTUS case.

But here's why I think Myriad STILL is the gold standard.

A. They have the experience doing this testing
B. They have the infrastructure to handle national samples
C. They have the ability to analyze rare variants best. Why? They have the samples.....

That being said, could Quest or LabCorp begin BRCA testing? Yes and they would do a hell of a job.

One thing is for certain, Myriad will have a hard time justifying that 3120 USD price tag.

If you have MYGN maybe a short is in store?

The Sherpa Says: Myriad is how a genetics lab should be run, except for the outrageous price.

PGx in DTCG? Doesn't stand up to Useful testing.

2010-03-24T04:38:00.000-07:00

HT Don Rule today as well as the ENTIRE Pharmacogenomics Advisory Group that I am a proud member of.

Don wrote this comment a few days ago

"I was curious about what SNPs the DTC companies offer so I wrote a little applet (http://snpweb.cloudapp.net/#/PharmGKBSNPs) to compare them to the SNPs in PharmGKB. It turns out the the Cytochromes are particularly sparse."

Well Don, you are correct. Even more so, as we began to review SNP data it became crystal clear on Monday.

The reason I was pissed about 23andMe doing the CF testing is because they missed hundreds of potential carrier alleles. What was even more so angering when I realized, you could be "tested" by one of these DTCG companies for "Plavix Metabolism" and come up with the absolute wrong answer.

Imagine that. Most people turn to DNA for an "absolute call" but when you don't look for the right SNPs or all of the needed SNPs, you miss a whole bunch.

Quick story. I had this pulmonologist physician, an elder statesman, super smart, Ivy league trained come up to me and say "Hey Steve, can you help me out?"

He is a sleep doctor too. He said "I have been trying to test for this narcolepsy gene and I can't get the right answer"

I said "Sure Dr. X, what do you mean 'keep getting the wrong answer'?"

He Said

"Well I am looking for HLA DQB1 and they keep telling me about this HLA DR, I have sent this test 3 times now and still gotten no information about HLA DQB1."

I did a big 'ol face palm.

Quest, where he had sent the blood, did not test for HLA DQB1

Instead it searched for an imperfect haplotype......

That's the problem. If you don't test for exactly what you are looking for, you will never find it. Nor will you have the correct clinical answer.

If you only test 2 SNPs for CYP 2C19, you will never be able to accurately predict what someone's metabolizer status is.

What people should be using to assess metabolizer status of medications is something like the DMET Plus with additional PCR or another platform. AmpliChip does a nice job, but we have to be serious when it comes to medical care.

You Cannot, I repeat Cannot take the advice from 23andMe when it comes to metabolizer status for Plavix.

Please, please, please listen to me. Even 23andMe states it on their post about Plavix

This DTCG test is not ready to be used in the clinic or even trusted to tell your metabolizer status. Right now, they are not testing enough SNPs for me to be happy with it and use it in the office.

Don't stop your Plavix! Instead go get a clinical pharmacogenomic test done by someone who understands the limitations of the labs.

That drunk who lost their keys is still looking under the lamposts because that is where the light is..........

That is a stupid way to do clinical pharmacogenomics.

The Sherpa Says: Pretending to be clinical without standing up to clinical rigor is a recipe for disaster. I await the lawsuit from in stent thrombosis for the poor sap that trusts 23andMe enough to stop their Plavix.

Why did P&G invest in Navigenics?

2010-03-23T12:36:00.000-07:00

I kept beating myself up, trying to figure out why the largest food/products company in the world put money in Navigenics. Was it for nutrigenomics? Was it for the captive audience to market products to?

Until today, when I read in American Medical news that Proctor and Gamble BOUGHT MDVIP in December of last year! Man how did I miss that one?

"Terms of P&G’s acquisition were not disclosed. It was made by P&G’s FutureWorks unit, a new-business generator that’s intended to connect the company with external partners and expand P&G’s scope beyond its core businesses into new channels."

So, P&G is looking for the whole enchilada in personalized medicine here.

Too bad, Navigenics' tests are currently not useful. But maybe someday they will be......

The Sherpa Says: Navigenics is not the target. MDVIP was, so don't believe anyone who tells you otherwise...

A moment of Clarity. Some DTCG is not bad.

2010-03-18T05:52:00.000-07:00

Ok,

Here is the G-d's honest truth. Not all SNP/DTCG companies are bad. What do I mean by bad?

Not all SNP/DTCG companies misrepresented that which is not medically useful as medically useful.

I look at Pathway and Counsyl for example. Fast followers looking to say what they do and mean what they say.

Some of these DTCG tests could be clinically relevant and useful. The problem I have, is that there is no point at which I can say, "Hey I just want the clinically relevant stuff!" No ear wax please.

I need that as a clinician. If I want a huge panel of say CYP450 tests, where do I go? there are some labs that do this and charge and arm and a leg. One company, who I used charged the patient thousands of dollars because insurance wouldn't pick it up.

That cannot ever happen again.

With the addition of these tests with some clinical value, there must be a value add of inexpensive and RAPID TAT (Turn Around time)

A classic example is my last post. Provided these tests become validated clinically, in a patient who can't give me her Gail risk information (tough not to, but it could be a real case) I would use that other panel

The same is true for BRCA founder mutations. Provided you won't drop it in some google database that they get served up mastectomy ads, some patients are afraid of needles and that is a barrier.

There are some very good things here. These good things are getting drowned out by some very bad things.

We can work together if you are willing to bend.

Keith Grimaldi said it best on his blog

"The lack of really effective clinical utility and the existence of commercial interests increases the confusion though. It’s hard to sell something that is interesting, “fun”(?), quite expensive, but not actually that useful to the majority right now. Hard to sell means sometimes over the top marketing."

What medicine cannot tolerate is Over the Top Marketing. It leads to inaccurate statements. This is something extremely forbidden in certain states. In fact, some states don't allow advertising to patients at all, or there laws are so strict you couldn't say anything than

"Dr Murphy, accepting new patients, take insurance"

Why is this? It is to prevent false claims and promises. Doctors can't make money back guarantees. They can't make statements which are not based on fact in advertising. A lot of companies in a rush to get out young science and feed the hype cycle for grants and whatever have been all too guilty of this hype.

So when I get a comment from one of my readers who says (paraphrased)

"Hey all this bashing you do on DTCG is making us in the science end of the SNP reseach look bad"

It prompted me to say, hey, I wouldn't have to throw so much cold water on it if it weren't being hyped so much by DTCG.......

So I guess my point is simple.

Hey DTCG, your opportunity is to leverage your amazing platforms to launch medical services, TO and WITH physicians.

Keep the nonmedical exactly that, NONMEDICAL

Keep the Medical EXACTLY that, MEDICAL

People can benefit by knowing their 2D6/2C19/2C9/VKORC1.

But there are some hurdles to be overcome

1. How can I trust your results?

You have started by enlisting or creating CLIA certified labs, that is a good start. Maybe FDA cert would be nice. Not needed, but nice. There currently is only AmpliChip that is FDA approved....Would like others.

2. How can I know your interpretation is correct?

By using board certified molecular pathologists, I can get a comfortable feel for the fact that the results have been vetted by your specialist. This is muy importante!

3. How can I integrate the results into my EMR/PHR/etc.?

This is going to be super important. How can I save these results linked to patient care? Sure, some would pull paper and put it in the chart, others would prefer a pull in and link. You have to think how to do this.

4. What if the interpretation changes?

Will you take responsibility to contact Either the ordering physician or patient when a result changed? This will be important as we learn more about the nature of these genetic changes.

Doctor's rely on these 4 things from most labs that they use. The depend on these services to be provided professionally and accurately.

These 4 things are EXTREMELY hard to do. But NEED to be done if you really want to be a part of the medical community. But even if you don't, I think your customers deserve this sort of validation and service. Don't you?

Take the jump, create a medical arm. Work with us.

The Sherpa Says: This is what is needed. Medicinally used DTCG that is "Allowed" to be of clinical use. A new Terms of Service, just for doctors, with a validation process that is transparent. And a Marketing process which is truthful.

How can MDVIP use Navigenics Test for Medicine?

2010-03-17T05:54:00.000-07:00

I have been harping on this say what you mean. Say what you do. Theme lately.

I am a board certified doctor who practices personalized medicine. I see patients and apply the principles or pharmacogenomics, risk prediction and prevention tailored to each individual patient. I do this by taking a 3 generation pedigree, using current clinical risk models and pharmacogenomic or other genetic tests when indicated. That's me.

I have this nagging pain about MDVIP, Ed Goldman and Navigenics.

Some MDVIP members are using Navigenics tests for medical risk prediction. Navigenics is ok with this because hey, they're doctors.

But I have a problem. The only terms of service I see here for Navigenics is listed and reads

The contents of our Site, including any risk estimates or other reports generated by the Services (collectively, "Your Report") and any other information, data, analyses, editorial content, images, audio and video clips, hyperlinks and references (collectively, "Content"), are for informational purposes only and are not intended to substitute for professional medical advice, diagnosis, or treatment.

The part I want to focus on is "Are for informational purposes only and are not intended to substitute for professional medical advice, diagnosis or treatment"

It seems to me that this will be the more popular language in a Terms of Service for DTCG.

Notice that nowhere does it say, "This report is not intended to diagnose or treat"

I think that while it is nice to not say that, when in fact people are using it to diagnose, it is even goofier to say that it is not intended to substitute for a professional's diagnosis. Ok, so are you saying

1. This is not to be used for diagnosis/medical advice

2. This is to be used for diagnosis, but the professional's diagnosis trumps ours

3. This test is meant to be used by professionals to aid them in diagnosis and treatment

I am really confused here. Is this a medical test or not. Just come right out and say it!

The Sherpa Says: Say what you do, do what you say you do. Isn't that what the Common Framework of Principles is About?

SNPs for breast cancer risk? It Depends.

2010-03-17T04:39:00.000-07:00

I hold in my hot little hands a copy of the NEJM, March 18th edition. In it there is an article which isn't even released yet.

Entitled

"Performance of Common Genetic Variants in Breast-Cancer Risk Models"

Remember when we did this for heart disease risk? FAIL WHALE.....

Do you think it will happen again?

The Study

10 common genetic variants

I had to create a couple of pages on SNPedia for this list FYI.....

The Methods:

Cases and controls-WHI, ACS CPSII Nutrition Cohort, Nurses Health Study, Prostate/Lung/Colorectal/Ovarian Cancer Screening Trial, and Polish Breast Cancer Study.

Cases-Woman who had received diagnosis of invasive breast cancer.

Risk Models Used-A hybrid of the Gail model.....I.E. Not exactly the Gail Model.

1. First degree relatives with breast cancer

2. Age at Menarche

3. Age at first live birth

4. Number of Breast Biopsies

They acknowledge that they were unable to get atypical hyperplasia and Mammographic density. Both of which have improved Gail.

So, This Gail is a little hobbled and not the best predictive model.......

The studied models- 5 logistic regression models

I don't have the supplementary tables and methods yet.

The nongenetic model-Gail Model

The Demographic/Genetic Variant Count Model-included number of alleles.

The Demographic/Genetic Individual Variant-Accounted for individual effects of each SNP

The Inclusive Model-Gail, Genetics Demographics

The Demographic Model

And Random....

When we do these sorts of statistical analyses we look for a couple of things.

A. Number of people reclassified and how?

B. The Area Under the ROC Curve

The AUC is a good way of seeing whether a model or test is worthless or useful. And how much MORE useful than another test.

Results-

1. The Inclusive Model Yielded and AUC of 61.8%

2. The Nongenetic Model yielded an AUC of 58%

3. The Genetic Individual Variant Yielded an AUC of 59.7%

4. The Genetic Variant Count Yielded an AUC of 58.8%

5. Breast Biopsy BY ITSELF Yielded an AUC of 56.2%

That is a 3.8% difference in Yield from Genes and without Genes integrated into the weaker Gail Model.

Lastly, they asked. Well, does this Inclusive Model do a good job of discrimination of High risk vs. low risk.

The Answer- It determines lower risk better than Gail. It does not determine higher risk better.

The authors of this study have stated that

"As in Diabetes and cardiovascular disease, the addition of the common SNPs added little to the predictive value of the clinical models. On the basis of theoretical models, Gail has shown that increases in the AUC similar to those observed here and not sufficiently large to improve meaningfully the identification of women who might benefit from tamoxifen prophylaxis or screening mammography"

Take Home

The addition of these factors only creates a minimal statistical increase that is of no useful clinical benefit.

The Sherpa Says: If the press says "gene tests fail to improve risk assessment" You can be assured that the DTCG industry is no longer the darlings. If instead they say "Improvement in risk model" well, then you have chance to woo them back! It Depends.......

The Argument Against DTC Genomics Marketing and such

2010-03-16T05:16:00.000-07:00

Keith Grimaldi and Daniel MacArthur and Andrew Yates and I have a little bit of confusion. I think we are arguing over 2 different points.

First, Keith, Daniel and Drew need to go read a paper I authored entitled

"In Need of a Reality Check" published in the May 2009 Nature Biotech Journal.

I think many people have misunderstood our messages. So to be simple.

A. Keep the Medical, Well, Medical.

1. Medical Genetic tests that are to be used clinically should have clinical input
2. Medical Genetic tests should be regulated according to the laws of each state/country
3. DTC Genomic tests come in several flavors. The DTCG Medical tests should be Medical.

I have been championing this one for a LONG time. The arguments for this are pretty clear

1. Without clinical input, selling medical tests without an understanding of their use on a FIRST HAND basis is a bad business plan. Also, the risks of a non physician over marketing these tests as to be used for too many things or used before the science pans out could harm the consumer. Think OvaSure......

How? Via false advice and guidance, delivered not by a physician, but by a website.
Who takes accountability and liability for this? The answer no one. Thus, the chain of trust is broken and the patient is left no recourse.

2. Medical Genetic Tests should be regulated by the laws of the country/state/province of use.

Why? Well, if we don't agree to follow laws, we are lawless. How does being lawless benefit the consumer/patient? How does it build trust? It doesn't, thus, EVEN IF the laws are "stupid and outdated" those who break the law, break the trust required for such special testing and care.

3. Medicinally used genetic tests, whether DTCG or not, should be represented and treated as Medical Tests.

Why? This goes back again to quality control and tests. This also goes back to trust. If a patient is encouraged to use a medicinally used genetic test, they should have the confidence that it meets medical quality and that the lab follows that are required for medical tests.

Am I wrong? I challenge someone to give me 3 good reasons why these rules should not be followed. And they cannot use "We are slowing innovation" "It is inevitable" or "You are rent seeking doctors" Why? these are stupid arguments that you will need to prove beyond a shadow of a doubt. Why? When patient safety and trust is one the line, you better be DAMN sure of your stance.

B. The marketing of these current DTCG tests in not keeping medicinally used tests in the medical realm. They should immediately correct this course.

1. Marketing message confusion leads people to equate nonmedical tests as medical. This results in the customer/patient. relying on non-standard of care tests.

I use here the example of Dane Jasper an SV entrepreneur who said he could save "25 bucks" buy relying on 23andMe's CF test instead of going to a trained professional to have testing done.

2. Simply stating your tests are "nonmedical" does not make them "nonmedical" especially if they have a long history of being used medically.

May I skip getting licensed in a state if I say I do "nonmedical" medicine? May I give you coumadin "OTC" if it is to not be used to diagnose or treat a condition? No, I may not. Can someone OTHER than a pharmacist/doctor get access to medications? Not in the US.

They do this to avoid charlatanism and people putting other people at risk. In this case, the risk is a "nonmedical" diagnosis of CF carrier state, or a "nonmedical" misdiagnosis of no CF carrier state.

3. Marketing "NonMedical" Medical tests as cool and hip

A. Turns off doctors from using useful tools

B. Makes the valued noble profession of medicine appear, trivial, akin to Paris Hilton.

Please stop this now.

The Sherpa Says: This is too long to have in a post. I am drafting a paper on this subject now. But you first should read "In Need of A reality Check" in Nature Biotech.

BRCA testing by 23andME is the same as Myriad Genetics.

2010-03-14T16:03:00.000-07:00

February 2009 23andMe entered into clinical medical testing of DNA variants which are the exact same variants Myriad Genetics tests for. There is only ONE use for this test. That is a clinical use. When these results are obtained clinical counseling is the standard of care for delivery of these results. Not a flashy webportal......

Minimizing the seriousness of a medical test looked just as awkward by us in the first video as it should be by showing it on a blimp or at a cocktail party or highway billboard sign.....All things that Linda Avey and Anne Woj decided to have their company do....

The Sherpa Says: Misha is correct, Medical Geneticists painted themselves into a corner by harboring in the rare disease port. This allowed people who have no G-dDamn business in medicine, to play doctor at parties and on the internet!